UC-NRLF 


3m 


THE  LIBRARY 

OF 

THE  UNIVERSITY 
OF  CALIFORNIA 


PRESENTED  BY 

PROF.  CHARLES  A.  KOFOID  AND 
MRS.  PRUDENCE  W.  KOFOID 


SMITHSONIAN  CONTRIBUTIONS  TO  KNOWLEDGE. 

-     647     — 


RESEARCHES 


VENOMS  OF  POISONOUS  SERPENTS. 


BY 

S.  WEIR(_MITCHELL,  M.  D., 

.MEMBER  OK  THE  NATIONAL  ACADEMY  OF  SCIENCES,    F.   S.    A.  ;    PRESIDENT  OF  THE  COLLEGE  OF  PHYSICIANS 

OK  PHILADELPHIA. 


EDWARD  T.  REICHERT,  M.D., 

PROFESSOR  OF  PHYSIOLOGY  IN    THE    UNIVERSITY  OF   PENNSYLVANIA. 


[ACCEPTED    FOR    PUBLICATION,    MAY,    1885.] 


WASHINGTON: 
PUBLISHED   BY    THE    SMITHSONIAN   INSTITUTION. 

1886. 


COMMISSION 

TO    WHICH    THIS    MEMOIR    HAS    BEEN    REFERRED. 

JOHN  S.  BILLINGS,  M.  D., 
HENRY  G.  BEYER,  M.  D. 

SPENCER  F.  BAIRD, 

Secretary  S.  I. 


COLLINS  PRINTING  HOUSfi, 
PHILADELPHIA. 


PREFACE. 


THE  authors  desire  to  express  their  multiple  obligations  to  the  Smithsonian 
Institution.  They  have  to  thank  the  Army  Medical  Library  for  the  valuable 
Bibliography  appended  to  this  essay.  With  that  to  be  found  in  Dr.  AVeir  Mitchell's 
former  essay,  it  completes  the  list  of  such  knowledge  up  to  January,  1885.  They 
desire  also  to  thank  Her  Britannic  Majesty's  Indian  Government  for  help  in  secur- 
ing Indian  serpent  poisons.  Among  individuals  they  owe  to  no  one  so  deep  a  debt 
as  to  Vincent  Richards,  Esq.,  of  Goalundo,  British  India.  Without  his  untiring 
aid  the  authors  feel  that  it  would  have  been  impossible  to  have  extended  their 
inquiries  beyond  our  native  snakes. 

The  excellent  plates  were  drawn  for  the  most  part  by  Dr.  J.  Madison  Taylor, 
and  thanks  are  due  to  Dr.  Geo.  A.  Piersol's  skill  for  the  interesting  micro- 
photographs  of  blood-corpuscles  attacked  by  venom.  The  authors  are  also  indebted 
to  Dr.  Guy  Hinsdale  for  having  made  the  tabulated  reductions  of  kymographion 
tracings. 

S.  WEIR  MITCHELL, 
EDWARD  T.  REICHERT. 

PHYSIOLOGICAL  LABORATORY  OF  THE 
UNIVERSITY  OF  PENNSYLVANIA. 


(Hi) 


TABLE  OF  CONTENTS. 


PAGE 

PREFACE  ..........         iii 

LIST  OF  ILLUSTRATIONS  ........  ix 

INTRODUCTION  .  .  .  .  .  .  .  .  .  .1 

CHAPTER  I. 
PHYSICAL  CHARACTERISTICS  OF  VENOM          .......          5 

CHAPTER  II. 

THE  CHEMISTRY  OF  VENOMS  .  ....  9 

CHAPTER  III. 

THE  EFFECTS  OF  VARIOUS  AGENTS  ON  VENOM  ......         21 

CHAPTER  IV. 

THE  EFFECTS  OF  VENOM  WHEN  APPLIED  TO  Mucous  OR  SEROUS  SURFACES  .  .  .44 

CHAPTER  V. 

THE  EFFECTS  OF  VENOM  ON  THE  NERVOUS  SYSTEM  ......        48 

CHAPTER  VI. 

THE  GLOBULINS  AND  PEPTONES  COMPARED  AS  REGARDS  LOCAL  POISONOUS  ACTIVITY  .        51 

CHAPTER  VII. 

THE  ACTION  OF  VENOMS  AND  THEIR  ISOLATED  GLOBULINS  AND  PEPTONES  UPON  THE  PULSE- 
KATE  56 


Section  I. — The  action  of  pure  venom  upon  the  pulse-rate  .  .  ... 

The  action  of  pure  venom  upon  the  pulse-rate  of  normal  animals 
The  action  of  pure  venom  upon  the  pulse-rate  in  animals  with  cut  pneumo- 


56 
57 


gastric  nerves          ......  63 

The  action  of  pure  venom  upon  the  pulse-rate  of  animals  in  which  sections  of 
the  pneumogastric  nerves  and  of  the  upper  cervical  portion  of  the  spinal 
cord  had  been  made  .  .  .  .  .  .  .66 

' 


vi  TABLE   OF   CONTENTS. 

PAGE 

Section  II The  action  of  venom  globulins  upon  the  pulse-rate  .  .  .  .69 

The  action  of  venom  globulins  upon  the  pulse-rate  of  normal  animals  .  69 

The  action  of  venom  globulins  upon  the  pulse-rate  of  animals  with  cut  pneu- 

mogastric  nerves     ........         74 

The  action  of  venom  globulins  upon  the  pulse-rate  of  animals  with  the  pneu- 

mogastric  nerves  and  cervical  .spinal  cord  cut          ...  16 

Section  III. — The  action  of  venom  peptones  upon  the  pulse-rate  ...  79 

The  action  of  venom  peptones  upon  the  pulse-rate  of  normal  animals  79 

The  action  of  venom  peptones  upon  the  pulse-rate  of  animals  with  cut  pneu- 

mogastric  nerves    ......  82 

The  action  of  venom  peptones  upon  the  pulse-rate  of  animals  with  the  pneu- 

mogastric  nerves  and  cervical  spinal  cord  cut         .  .  .  .83 

CHAPTER  VIII. 

THE  ACTION  or  VENOMS  AND  THEIR  ISOLATED  GLOBULINS  AND  PEPTONES  UPON  THE  ARTE- 

KIAL  PRESSURE         .  .  .  .  .  .  .  .  .85 

Section  I. — The  action  of  pure  venom  upon  the  arterial  pressure  .  85 

The  action  of  pure  venom  upon  the  arterial  pressure  of  normal  animals  .  85 

The  action  of  pure  venom  upon  the  arterial  pressure  of  animals  with  the 

pneumogastric  nerves  cut  .......         92 

The  action  of  pure  venom  upon  the  arterial  pressure  of  animals  with  the 

pneumogastric  nerves  and  cervical  spinal  cord  cut  .  .  .95 

The  action  of  pure  venom  upon  the  arterial  pressure  of  animals  with  the 

pnenmogastric,  depressor,  and  sympathetic  nerves  and  spinal  cord  cut  98 

Section  II. — The  action  of  venom  globulins  upon  the  arterial  pressure      .  .  .       102 

The  action  of  venom  globulins  upon  the  arterial  pressure  of  normal  animals        102 
The  action  of  venom  globulins  upon  the  arterial  pressure  of  animals  with 

pneumogastric  nerves  cut   .  .  .  .  .  .  .107 

The  action  of  venom  globulins  upon  the  arterial  pressure  of  animals  with 

pneumogastric,  depressor,  and  sympathetic  nerves  and  spinal  cord  cut       .       109 

Section  III. — The  action  of  venom  peptones  upon  the  arterial  pressure       .  .  .112 

The  action  of  venom  peptones  upon  the  arterial  pressure  of  normal  animals        112 
The  action  of  venom  peptones  upon  the  arterial  pressure  of  animals  with  the 

pneumogastric  and  depressor  nerves  cut    .....       114 
The  action  of  venom  peptones  upon  the  arterial  pressure  of  animals  with  the 
pneumogastric,   depressor,   and   sympathetic   nerves   and   cervical   spinal 
cord  cut     .  .  .  .  .  .  .  .  .116 

CHAPTER  IX. 

THE  ACTION  OF  VENOMS  AND  THEIR  ISOLATED  GLOBULINS  AND  PEPTONES  UPON  RESPIRATION       119 

Section  I. — The  action  of  pure  venom  upon  the  respiration          .             .             .  119 
The  action  of  pure  venom  upon  the  respiration  of  normal  animals     .             .  119 
The  action  of  pure  venom  upon  the  respiration  of  animals  wkh  the  pneumo- 
gastric nerves  cut  .             .             .             .             .             .             .  122 

Section  II. — The  action  of  venom  globulins  upon  the  respiration  .             .                          .  125 
The  action  of  venom  globulins  upon  the  respiration  of  normal  animals         • .  125 
The  action  of  venom  globulins  upon  the  respiration  of  animals  with  the  pneu- 
mogastric nerves  cut                        .             .  129 


TABLE    OF   CON  TE  NTS  vii 

PAGE 

Section  III. — The  action  of  venom  peptones  upon  the  respiration  ....  130 

The  action  of  venom  peptones  upon  the  respiration  of  normal  animals           .  130 
The  action  of   venom  peptones  upon  the  respiration  of  animals  with  the 

pneumogastric  nerves  cut    ...                        ...  131 

CHAPTER  X. 

PATHOLOGY                                                                                          .                        .  133 


CHAPTER  XI. 

GENERAL  CONSIDERATIONS     .........  153 

BIBLIOGRAPHY  .......  ...  159 

DESCRIPTION  OP  PLATES         .........  181 

INDEX  .  .  183 


LIST  OF  WOOD-CUTS. 


PAGE 

Figure  1.  Snake  loop                        .             ...  .  3 

Figure  2.  Venom  dried        .....  ...  5 

Figure  3.  Muscle  tissue  altered  by  venom    ...  ...  147 

Figure  4.  Muscle  tissue  altered  by  venom   ...  .  147 


(ix) 


INTRODUCTION. 


A  FEW  words  of  explanatory  character  in  regard  to  the  following  essay  may 
not  be  out  of  place.  From  the  time  of  Fontana,  1767,  until  the  able  essay  of 
Lucien  Bonaparte,  in  1843,  on  the  chemistry  of  venom,  there  was  no  paper  of 
moment  on  serpent  poisons.  In  January,  1861,  one  of  us,  S.  Weir  Mitchell, 
published  a  long  study  of  the  venom  of  the  Crotalus  durissus,  and  in  1868  sup- 
plemented it  by  a  shorter  contribution,  in  which  he  related  some  recent  discoveries 
of  his  own.  and  corrected  certain  errors  of  his  former  paper.  These  two  essays 
may  be  considered  as  constituting  with  Lucien  Bonaparte's  the  foundation  of  the 
later  work  in  this  direction,  and  perhaps  as  having  left  the  study  of  venoms  in  as 
definite  a  position  as  could  be  gained  with  the  laboratory  facilities  of  1843  to  1868. 

In  1872,  the  government  of  India  enabled  Sir  Joseph  Fayrer  to  publish  a  volume 
of  beautiful  plates  of  the  venomous  snakes  of  India,  to  which  was  appended  also 
a  series  of  investigations  into  the  toxicology  of  their  poisons.  In  1872  the  same 
author  and  Dr.  Lander  Brunton  contributed  an  admirable  physiological  study  of 
the  effects  of  venoms.1 

In  1874,  Vincent  Richards,  as  chairman  of  a  government  commission,  published 
an  excellent  report  on  antidotes. 

Dr.  Wall's2  thoughtful  and  suggestive  book  appeared  in  1883.  It  is  a  compara- 
tive study  of  the  poisons  of  the  colubrine  and  viperine  serpents  of  India. 

These,  with  a  too  brief  study  of  the  poison  of  our  copperhead  by  Dr.  Isaac 
Ott,  of  Easton,  Pennsylvania,  sum  up  all  of  value  which  has  been  added  to  the 
physiological  literature  of  this  most  interesting  subject. 

Why  it  has  won  so  few  investigators  is  not  far  to  seek.  Even  in  India,  where 
the  appalling  loss  of  life  from  snake-bites  has  of  late  invigorated  research,  the 
power  and  means  of  government  were  needed  to  overcome  the  obstacles  which 
surround  such  scientific  effort  from  inception  to  close.  But,  if  in  a  land  where 
snakes  abound  and  professional  snake-catchers  can  be  had,  it  is  yet  not  easy  to 
follow  this  pursuit  with  success,  elsewhere  it  is  a  task  set  about  with  inconceivable 
obstacles.  The  fear  of  serpents,  the  rarity  of  some  species,  the  distances  to  which 
they  have  to  be  carried,  the  mortality  of  caged  specimens,  and  the  great  cost  of 

1  Proc.  Roy.  Soc.  1812,  1873,  and  1875. 

a  Indian  Snake  Poisons;  their  Nature  and  Effects.     A.  J.  Wall,  M.D.,  F.R.ColJ.S.,  1883. 

1        April,  1886.  (    I     ) 


2  INTRODUCTION. 

purchase  and  transportation,  need  only  to  be  mentioned  as  indicating  our  own 
difficulties.  What  had  been  done  in  India,  sustained  by  a  government,  had  to 
be  with  us  attempted  by  private  individuals,  aided  by  the  Smithsonian  Institu- 
tion, without  which  it  would  have  been  impossible  to  succeed.  Our  work  began 
in  the  autumn  of  1882,  by  extended  efforts  on  our  part,  and  that  of  the  Smith- 
sonian, to  buy  or  otherwise  get  numerous  living  specimens  of  the  American  genera 
of  Thanatophidese.  This  quest  was  kept  up  by  every  means  our  ingenuity  could 
devise,  and  neither  time  nor  money  was  spared.  We  succeeded  in  obtaining 
a  sufficient  number  of  rattlesnakes,  including  Crotalw  adamanteus  and  C.  durissus. 
We  have  had  also  enough  of  the  Moccasin  (Ancistrodon  piscivorus).  Our  wants  as 
regards  Ground  Rattlesnakes,  Copperheads,  and  Coral-snakes  have  been  less  com- 
petently supplied,  chiefly  because  these  snakes  are  all  small,  so  that  to  get  enough 
of  their  poison  for  study  it  was  essential  to  have  a  great  many  snakes.  We  have 
had  in  all  about  two  hundred  living  serpents,  and  among  them  some  superb 
specimens,  which  yielded  poison  in  large  quantities.  Thus  one — C.  adamanteus — 
was  eight  and  a  half  feet  long  and  weighed  nearly  nineteen  pounds.  It  furnished 
on  one  occasion  about  one  and  a  half  drachms  of  venom. 

It  was  thought  desirable  by  Prof.  Baird  and  ourselves  to  examine  the  poisons  of 
Indian  serpents.  To  secure  these  the  Secretary  of  State  appealed  to  Her  Majesty's 
Indian  government  in  our  behalf.  A  courteous  response  was  returned,  and  orders 
given  which  resulted  in  our  receiving  a  certain  amount  of  Cobra  venom.  A  more 
constant  and  larger  supply  was  due  to  the  generous  and  untiring  kindness  of 
Vincent  Richards,  Esq.,  M.R.C.S.,  of  Goalundo,  B.  I. 

The  poison  of  the  Daboia  Russell ii,  the  Indian  viper,  we  sought  in  vain  to 
secure.  Government  aid  and  private  enterprise  alike  failed  to  secure  a  sufficient 
quantity  of  the  venom  of  this  dreaded  reptile.  The  other  Thanatophidea?,  of 
Australia,  and  South  America,  still  await  more  careful  study,  and  our  preliminary 
report  has  already  been  the  means  of  renewing  interest  in  the  chemical  aspects  of 
this  study  in  India. 

Such  of  our  serpents  as  were  not  cared  for  by  the  hospitality  of  the  Philadelphia 
Zoological  Garden,  were  kept  in  large  boxes,  about  four  and  a  half  feet  high, 
covered  on  top  with  removable  wire  network,  and  well-ventilated  through  wired 
openings  below.  They  were  of  course  furnished  with  water,  and  if  they  declined 
to  eat,  were  fed  at  intervals,  by  artificial  means,  with  raw  beef  chopped  fine,  and 
passed  down  into  the  belly  of  the  snake  through  a  large  glass-tube.  Under  this 
treatment  the  deaths  were  fewer,  and  the  supply  of  venom  far  better.  Probably 
this  method  could  be  usefully  employed  in  zoological  gardens,  where  many  snakes 
are  lost  owing  to  their  indisposition  to  feed  during  the  early  months  of  captivity. 

On  all  occasions,  for  forced  feeding,  or  for  the  purpose  of  extracting  venom,  the 
snakes  were  caught  and  held  in  the  snake  loop,  Fig.  1.  This  is  merely  a  staff, 
having  a  leather  strap  so  arranged  that  it  can  be  drawn  out  into  a  loop  in  which 
the  serpent's  neck  is  noosed,  and  so  held.  With  this  simple  means  all  risk  is 
avoided,  and  with  it  serpents  of  any  size  and  strength  to  be  met  with  among  our 
Thanatophidea?  can  be  safely  held  and  easily  manipulated. 

For  whatever  reasons  the  study  of  snake  venoms  had  not  greatly  advanced  since 


INTRODUCTION.  3 

the  last  research  of  Fayrer  and  Lander  Brunton  until  the  authors  of  this  paper 
resumed  the  work  in  1882.  One  of  them  (Dr.  Mitchell)  hud  long  felt  that  it 
would  be  well  to  revise  the  toxicology  of  our  American  serpents  which  he  had 
begun  in  18o8,  and  as  the  later  English  observers  had  in  some  points  differed  from 

Fig.  1. 


him,  to  learn  if  they  or  he  were  correct,  or  whether  the  divergence  as  to  results 
was  due  to  variations  in  the  qualities  of  the  venoms  employed.  Then  too  he  had 
become  conscious  of  certain  errors  in  his  former  researches,  and  wished  to  aid  in 
correcting  them,  and  in  rilling  up  some  of  the  gaps  left  in  this  branch  of  toxi- 
cology by  himself  and  others. 

The  authors  started  with  a  theory  long  held  by  Dr.  Mitchell  that  snake  venoms 
are  not  simple  in  composition,  but  composed  of  two  or  more  poisonous  substances, 
and  that  in  the  qualities  and  quantities  of  these  agents  would  be  found  an  expla- 
nation of  the  differences  between  serpent  venoms  as  to  power  to  kill  and  mode  of 
causing  death. 

How  fertile  has  been  the  germinal  idea  of  this  research  must  be  judged  of  by 
this  present  essay;  which  will,  we  trust,  by  leading  thought  and  experiment  in 
new  directions  hasten  the  day  when  we  shall  be  able  to  treat  with  success  the 
wretched  thousands  who  now  perish  annually  by  snake-bite  in  India  and  elsewhere. 

Some  of  our  earlier  results  were  so  soon  talked  of  and  even  noted  in  public 
prints,  that  it  seemed  wise  for  this,  and  all  other  reasons,  to  state  what  we  then 
knew.  This  was  done  in  a  "  Preliminary  Report  to  the  United  States  National 
Academy  of  Sciences,  in  April,  1883."  In  this  brief  essay  we  announced  our 
proofs  of  the  complex  nature  of  snake  poisons.  The  report  was  incomplete,  and 
in  the  light  of  our  present  more  elaborate  essay  may  be  seen  to  contain  several 
erroneous  statements. 

It  is  not  in  the  nature  of  things,  that  a  research  along  such  varied  lines  as 
our  present  volume  follows,  though  extending  over  several  years,  should  be  per- 
fect in  detail,  or  complete  for  all  genera  of  Thanatophidians.  It  is  our  earnest 


4  INTRODUCTION. 

hope  that  it  will  be  complemented  and  supplemented  by  some  of  the  able  staff  of 
the  British  Army  Medical  Service  in  the  East  Indies.  There,  only,  is  it  possible 
to  find  enough  serpents,  and  all  the  various  species  which  it  will  be  desirable  tc 
review  lexicologically  from  the  new  stand-point  which  we  think  we  have  estab- 
lished. 

We  have  forborne  to  overload  this  paper  with  comments  on  the  later  researches 
of  others,  and  have  made  the  discussion  of  our  own  work  as  brief  as  was  consistent 
with  clearness. 

In  writing  of  the  various  substances  contained  in  venoms,  we  have  given  them 
names  which  are  fairly  descriptive,  but  which,  as  in  the  case  of  the  peculiar 
peptone  of  Cobra,  may  perhaps  excite  criticism.  Yet,  however  unsatisfactory  our 
method  of  nomenclature  may  be,  any  other  plan  of  naming  the  curious  bodies  in 
question  would  certainly  have  been  even  more  misleading. 


CHAPTER    I. 
PHYSICAL  CHARACTERISTICS  OF  VENOM. 

Physical  Characteristics  of  Venom. — All  serpent  venoms  are  more  or  less  alike 
in  appearance  when  fresh.  They  are  fluids  varying  in  color  from  the  palest  amber 
tint  to  a  deep  yellow.  Dr.  Wall  describes  the  Cobra  venom  as  being  occasionally 
colorless.  This  peculiarity  we  have  never  seen  in  the  fresh  poison  of  any  of  our 
serpents,  except  once  in  the  coral  snake ;  nor  can  the  venom  of  one  kind  of  snake 
be  distinguished  with  certainty  by  any  physical  peculiarity  from  that  of  any  other, 
however  remote  they  may  be  in  the  scale  of  being. 

When  a  fluid  venom  is  allowed  to  dry  slowly  it  presents .  no  specific  distinctive 
appearances.  If  desiccated  too  rapidly,  it  may  look  a  little  more  gray  and  opaque 
than  is  common,  but  usually  it  dries  into  a  beautifully  cracked  mass,  deceptively 
like  an  aggregation  of  crystals,  and  which  is  well  represented  in  Fig.  2. 

Fig.  2. 


In  this  state  it  is  in  solid  yellow  particles,  very  fragile,  bright  yellow,  trans- 
parent or  translucent,  and  seemingly  indestructible  by  time,  since  the  dried  venom 
of  the  rattlesnake,  for  twenty-two  years  in  Dr.  Mitchell's  possession,  proved  as 
poisonous  as  that  removed  yesterday.  It  is  equally  unaltered  by  solution  in 
glycerin,  which  keeps  it  permanently  in  unchanged  toxic  force,  as  we  shall  here- 


6  THE    VENOMS    OF    CERTAIN    THANATOPHIDE^E. 

after  point  out.1  Neither  does  it  appear  to  be  injured  when  dry  by  mingling  it 
with  pure  alcohol.  In  fact  any  of  these  three  means,  desiccation,  glycerin,  or 
alcohol,  preserves  it  well. 

When  fresh  venom  of  any  serpent  is  examined  with  the  microscope  it  often 
presents  a  variety  of  floating  bodies  which  seem  to  be  much  alike  in  all  cases,  and 
are  very  well  shown  in  the  plates  of  Dr.  Mitchell's  former  paper  and  in  Vincent 
Richards's  reports.  In  healthy  serpents,  but  lately  caged,  there  are  fewest  of 
these  solid  ingredients,  as  has  been  noticed  by  Richards,  by  Wall,  and  by  S.  Weir 
Mitchell.  The  question  of  the  toxicity  of  these  suspended  solids  has  again  drawn 
our  attention  to  them,  and  we  have  had  yet  more  careful  and  repeated  microscopic 
examinations  made  by  Prof.  Formad.  He  found,  like  other  observers,  that  the 
venom  of  the  more  vigorous  snakes  has  the  least  visible  solid  matter ;  but,  as  in  the 
use  of  the  fang,  the  mucus  and  floating  solids  of  the  mouth  must  be  considered, 
and,  as  in  collecting  venom  from  the  snake,  more  or  less  of  the  mouth  fluids  mingle 
with  the  venom,  it  was  thought  well  to  reconsider  the  nature  of  the  floating  solids 
from  the  point  of  view  of  toxic  activity.  For  the  better  study  of  the  solids  found 
in  venoms  we  examined  numerous  specimens,  and  placed  many  of  these  in  the 
hands  of  Prof.  Formad,  from  whose  notes  we  select  the  following  observations : — 

A  drop  of  fresh  venom,  taken  directly  from  the  Crotalus  adamanteus,  was  examined 
with  a  TV  Zeiss.  homog.  immersion  lens  ;  amplification  800  diameters.  The  most 
striking  appearance  which  first  meets  the  eye  is  a  granular  material  scattered  about 
in  masses  of  various  size  and  shapes,  resembling  those  formed  by  bacteria.  There 
are  also  seen,  in  some  cases,  a  few  oval  nucleated  red  blood-corpuscles,  some  leuco- 
cytes resembling  salivary  corpuscles,  and  others  corresponding  to  ordinary  white 
blood-corpuscles,  the  latter  cells  in  an  active  state  of  amoeboid  motion.  There 
were  also  observed  several  club-shaped  epithelial  cells  covered  with  fine  granular 
material. 

The  granular  matter  first  mentioned,  and  which  seems  to  form  the  main  solid 
constituent  of  the  venom,  consists  of  two  elements:  Larger  granules  of  an  animal 
or  albuminous  character,  and  a  fine  granular  material  of  vegetable  nature.  The 
albuminoid  material  is  made  up  of  minute  particles  ovoid,  or  somewhat  irregularly 
angular  in  shape,  measuring  about  T7^^  of  an  inch  in  their  longest  diameters. 
These  ovoid  particles  are  grouped  side  by  side,  from  two  to  twenty  in  each  collec- 
tion, and  are  arranged  so  as  to  form  single  or  double  rows,  or  more  often  aggregated 
into  irregularly  shaped  clusters,  which  vary  in  size  from  -gfa  to  -g^rnr  °f  an  nich ; 
the  smaller  masses  predominating.  The  particles  just  described  are  colorless, 
refracting,  and  in  general  give  the  impression  of  bacteria.  They  are,  however, 
distinguished  from  the  latter  in  that  they  do  not  multiply  in  cultures,  or  respond 
to  the  aniline  dye  test  for  bacteria. 

There  are  usually  numerous  bacteria  in  perfectly  fresh  venom.  All  the  smaller 
particles  and  granular  material  are  micrococci,  measuring  on  an  average  T7|7Tr  of 
an  inch  in  diameter,  are  perfectly  round  or  somewhat  ovoid,  and  occurring  singly, 

1  Dr.  Mitchell  possessed  a  glycerin  solution  which  was  toxic  after  twenty  years. 


PHYSICAL    CHARACTERISTICS    OF    VENOM.  7 

in  pairs,  or  in  zooglcca  masses.  They  arc  less  refracting,  and  paler  than  the 
albuminoid  particles  described  above,  and  respond  promptly  to  the  usual  tests  for 
bacteria,  viz:  They  multiply  rapidly  and  absorb  well  the  aniline  dyes,  thus  form- 
ing a  marked  contrast  side  by  side  with  the  animal  granular  material,  which  was 
readily  discolored  under  the  influence  of  acid. 

The  epithelial  cells  seen  in  the  venom  are,  as  a  rule,  few  in  number,  are  squam- 
ous  or  club-shaped,  and  in  size  not  exceeding  that  of  the  red  blood-corpuscle  of 
the  serpent.  Leucocytes  are  also  few  in  number,  and,  as  well  as  the  epithelium,  are 
mostly  covered  with  micrococci.  A  few  of  the  white  blood-corpuscles  do  not  appear 
to  contain  micrococci,  and  in  fresh  venom,  especially  upon  the  warming  stage, 
exhibit  a  quite  active  amoeboid  motion.  The  venom  of  the  moccasin  presents  the 
same  appearances. 

If  fresh  venom  stands  but  a  short  time  exposed  to  the  air  the  micrococci  mulr 
tiply  with  remarkable  rapidity,  forming  large,  pale,  motionless  clouds ;  but,  in 
addition,  multitudes  of  movable  bacteria  (the  Bacterium  termo  and  a  bacillus — 
probably  Bacillus  sti-l>tU!*)  gradually  make  their  appearance.1 

The  globulous  masses,  above  described,  may  be  collected  by  filtration,  but  as 
this  is  often  a  difficult  or  even  an  impossible  process  with  a  fluid  as  viscous  as  pure 
venom,  and,  as  much  is  lost  in  the  filter,  another  method  was  devised,  and  there- 
after frequently  used  by  us  as  an  assistance  in  venorn  analysis.  A  tube,  about  5 
millimetres  wide  and  200  to  400  m.  m.  long,  has  a  bulb  blown  on  it  midway,  or  at 
the  top,  and  is  then  closed  above  in  the  blowpipe  flame,  and  strongly  heated 
throughout.  While  hot,  the  lower  end  drawn  to  a  point,  is  in  like  mariner  sealed. 
After  being  cooled  the  tip  is  broken  within  fresh  venom,  which  is  forced  up  into 
the  tube  by  atmospheric  pressure.  The  end  of  the  tube  is  then  once  more  adroitly 
sealed  in  the  flame. 

Thus  prepared  the  tube  is  suspended,  so  that  the  solids  of  all  forms  settle  in  a 
few  days,  while  for  this  time,  at  least,  the  venom  undergoes  no  such  putrefactive 
change  as  is  inevitable  when  it  is  exposed  to  the  air  at  our  ordinary  spring  or 
summer  temperatures. 

The  solids,  thus  collected  below,  are  easily  separable  from  the  supernatant  venom 
by  breaking  off  the  two  ends  of  the  tube  and  allowing  the  precipitate  to  escape, 
with  a  minimum  amount  of  liquid,  from  which  washing  in  water  easily  separates 
them. 

The  physical  appearances  of  the  venoms  of  the  moccasin  or  of  the  rattlesnake, 
tli us  secluded  from  the  air  in  these  partial  vacuum  tubes,  undergo  some  curious 
changes  of  much  interest. 

The  yellow  coloring  matter  disappears  from  below  upwards,  and  at  last  is  seen 
only  at  the  top,  where  the  venom  is  in  contact  with  the  small  amount  of  air  left  in 
the  tube.  At  first,  this  change  was  presumed  to  be  simply  the  rising  of  a  pigment 
of  lesser  gravity.  But  it  was  noticed  that  the  layer  of  yellow  was  of  no  deeper 
tint  in  its  lessened  bulk  than  when  diffused.  The  fluid  below  it  was  left  as 


1  Fresh  venom,  putrefied  from  long  standing,  appears  to  lose  at  least  a  portion  of  its  virulence. 
But  this  is  a  point  which  is  open  to  further  observation. 


8       THE  VENOMS  OF  CERTAIN  T H AN ATO P HI D E M. 

clear  and  tintless  as  water ;  but  when  re-exposed  to  the  air  once  more  became 
yellow  throughout,  within  one  or  two  hours. 

The  yellow  pigment  of  Cobra  poison,  when  the  dry  poison  was  dissolved  in  water, 
does  not  rise  in  the  tube  or  disappear,  but  remains  unaltered.  It  is  desirable  to 
repeat  these  observations  with  fresh  Cobra  venom. 

The  cause  of  the  disappearance  and  reappearance  of  the  coloring  matter  of 
venom  we  have  not  been  able  to  explain  to  our  satisfaction,  and  it  is  one  of  the 
questions  left  open  for  inquiry. 

The  Specific  Gravities  of  Venoms. — The  specific  gravity  of  the  venoms  of  our 
own  serpents  is  as  follows  :— 

Crotalus  horridus 1.054 

Crotalus  atrox  ........  1.077 

Crotalas  adaraanteus 1.061 

Ancistrodon  piscivorus      .......  1.032 

The  specific  gravity  of  Cobra  venom  is  given  by  Wall  at  1.058. 
As  to  that  of  the  Indian  viper  we  can  find  no  statement. 
The  losses  of  venom  on  drying  were  as  follows: — 

C.  adam.          .......       25.15  per  cent. 

C.  atrox 25.1(5       " 

Ancis.  piscivorus      .         .....       27.42       " 


THE    CHEMISTRY    OF    VENOMS 


CHAPTER    II. 

THE  CHEMISTRY  OP  VENOMS. 

THE  presence  of  alkaloids  in  venom,  and  especially  of  the  ptomaines,  has  been 
suspected,  and  these  bodies  have  been  repeatedly  sought  for  in  vain.  Gautier  is 
the  only  chemist  \ve  recall  who  asserts  that  he  found  a  ptomaine  in  a  venom 
(Cobra).  He  does  not  state  his  processes,  and  we  have  been  utterly  unable  to 
substantiate  his  statements.  Lest  we  should  in  some  way  have  erred  in  the  con- 
duct of  this  part,  of  our  labor,  we  asked  Prof.  Wolcott  Gibbs  to  examine  Crotalus 
venom  with  a  view  to  detection  of  such  a  body.  As  regards  this  search  he  makes 
the  following  statement : — 

"  My  investigation  of  rattlesnake  venom  had  for  its  special  object  the  comparison 
of  the  venom  with  the  higher  alkaloids.  As  the  quantity  of  material  at  my  com- 
mand was  small,  I  was  obliged  to  content  myself  with  the  application  of  the  ordi- 
nary tests  used  for  the  detection  of  alkaloids,  as,  for  example,  phospho-tungstates 
and  phospho-molybdates,  iodide  of  mercury  and  potassium,  etc.  etc.  In  many  cases 
precipitates  were  obtained,  but  these  were  in  no  case  distinctly  crystalline.  They 
resembled,  on  the  contrary,  the  precipitate  formed  by  sodic  phospho-tungstate  in 
solutions  of  albuminates  in  acetic  acid.  It  seems,  therefore,  very  improbable  that 
the  venom  contains  an  alkaloid  in  the  sense  in  which  that  term  is  commonly 
employed  by  chemists.  On  the  other  hand,  it  may  still  be  basic  in  character,  even 
if  it  be  classed  with  albuminoids,  since  these  are  known  to  combine  with  platinous 
cyanide  and  with  salicylic  and  other  acids,  exhibiting  the  properties  of  weak  bases 
as  well  as  of  weak  acids." 

Venoms  are  of  acid  reaction,  but  when  neutralized  we  have  not  observed  any 
precipitate  in  specimens  of  these  poisons. 

When  venom  is  taken  from  the  Crotalus  or  Ancistrodon  there  is  often  observed 
in  the  clear  poison  some  insoluble  whitish,  granular  matter,  which  soon  settles  to 
the  bottom. 

The  Insoluble  Precipitate. — This  insoluble  matter,  which  we  term  the  insoluble 
precipitate,  can  be  collected  for  examination  by  allowing  the  venom  to  stand  in 
hermetically  sealed  vertical  tubes,  as  previously  described.  The  precipitate  soon 
settles  to  the  bottom,  the  clear  venom  is  then  carefully  drawn  off,  and  the  precipi- 
tate is  repeatedly  washed  with  distilled  water  and  collected ;  the  washing  process 
is  repeated  until  there  is  no  trace  of  proteid  reaction  in  the  wash-water,  or,  in  other 
words,  until  all  of  the  soluble  portion  of  the  venom  has  been  completely  washed 
from  the  precipitate. 

When   examined  under  the   microscope   this  precipitate   consists  of  irregular 

2       April,  1886. 


10  THE   VENOMS   OF    CERTAIN   THANATOPHIDE^E. 

masses  of  granular  matter  with  epithelial  cells  and  salivary  corpuscles,  and  a  few 
flat  crystals  resembling  cholesterin. 

The  precipitate  gives  no  proteid  reactions  with  the  usual  proteid  color  tests,  is 
insoluble  in  neutral  saline  solutions,  and  in  weak  or  strong  acids  or  alkalies.  Boil- 
ing seems  to  render  the  mixture  clearer. 

When  injected  into  pigeons  this  precipitate  does  not  appear  to  possess  any  toxic 
properties. 

The  Globulins. — If,  after  the  separation  of  the  above  insoluble  precipitate,  the 
venom  be  mixed  with  water  and  placed  in  a  dialyser  over  running  water  it  will  be 
found  that  within  a  few  hours  a  whitish  precipitate  will  occur  within  the  dialyser, 
and  should  dialysis  be  continued  sufficiently  long  the  precipitate  will  have  become 
deposited  in  abundance.  If  the  precipitate  thus  formed  be  collected  on  a  filter  it 
will  be  found  that  all  of  the  coagulable  proteids  have  been  thrown  down,  since  the 
filtrate  now  yields  no  coagulum  by  brief  boiling,  although  it  gives  a  proteid  reaction. 

The  precipitate  is  now  washed  from  the  filter  and  subjected  to  repeated  wash- 
ings and  decantations  with  distilled  water,  until  the  wash-water  gives  no  proteid 
reaction.  This  purified  precipitate  is  found  to  give  reactions  peculiar  to  the 
globulins  ;  it  is  insoluble  in  distilled  water,  soluble  in  dilute  neutral  saline  solu- 
tions, soluble  in  dilute  acids  and  alkalies,  becomes  turbid  at  about  60°  C.,  and  is 
fully  coagulated  at  a  point  a  little  above  70°  C. 

The  filtrate  still  contains  some  proteid  in  solution,  since  we  find,  by  the  usual 
color  and  chemical  tests,  a  proteid  reaction,  although  it  is  observed  that  no  coagu- 
lation occurs  by  momentary  boiling.  The  filtrate  is  not  precipitated  by  strong  or  weak 
mineral  acids,  by  solutions  of  ferric  chloride  or  cupric  sulphate,  it  is  precipitated  but 
not  coagulated  by  absolute  alcohol,  and  if  placed  in  a  dialyser  it  will  be  found  to  be 
readily  clialysable.  These  reactions  it  will  be  observed  place  the  proteid  which 
remains  in  solution  in  the  filtrate  among  the  peptones.  But  we  shall  revert  to  this 
hereafter. 

It  will  thus  be  clear  that  we  have  separated  in  venom  representatives  of  two 
distinct  classes  of  proteids,  one  of  which  is  insoluble  in  distilled  water  and  coagu- 
lated in  solution  by  boiling,  and  another  which  is  soluble  in  distilled  water  and 
non-coagulable  by  brief  boiling;  the  former  belonging  to  the  (jlobulins  and  the 
other  to  the  peptones. 

The  substance,  however,  which  we  find  belonging  to  the  globulins  is  a  complex 
body  in  its  composition,  since,  by  appropriate  processes,  it  can  be  resolved  into  three 
distinct  principles,  each  of  which  is  a  globulin,  but  each  having  some  properties 
different  from  its  fellows.  In  order  to  distinguish  these  principles  AVC  have  named 
them  water-venom-globulin,  copper-venom-globulin,  and  dialysis-venom-globulin,  the 
names  indicating  the  principal  feature  of  the  processes  by  which  they  are  isolated 
from  each  other.  As  there  are  some  differences  in  the  reactions  of  similar  prin- 
ciples in  different  species  of  venoms,  we  shall  at  first  speak  only  of  the  venom  of  the 
Crotalus  adamanteus. 

Water-venom-globulin.— We  have  already  stated  that  when  a  solution  of  the 
fresh  or  dried  venom  in  distilled  water  is  allowed  to  stand  for  some  time,  especially 
if  the  quantity  of  water  be  comparatively  large,  a  whitish  precipitate  occurs  which 


THE  CHEMISTRY  OF  VENOMS.  11 

settles  to  the  bottom  of  the  glass,  leaving  in  the  course  of  a  few  hours  a  per- 
fectly clear  supernatant  liquid.  If  sufficient  water  has  been  added  at  first,  the 
addition  of  more  distilled  water  to  the  supernatant  liquid  will  not  cause  any 
further  precipitate. 

The  precipitate  is  now  collected  and  repeatedly  washed  with  distilled  water  and 
decanted  until  the  wash-water  yields  no  proteid  reaction. 

The  following  gives  the  results  of  some  of  the  many  reactions  upon  the  addition 
of  the  various  reagents  used '  — l 

Decided  reactions  with  the  usual  proteid  tests. 

Boiling — causes  coagulation. 

Sodic  chloride  (0  75  per  cent.) — slightly  soluble. 

'10       "         ) — soluble,  forming  a  turbid  solution  ;  the  solution  is  not  precipi- 
tated by  carbonic  acid'  nor  by  the  addition  of  ether. 

— boiling  the  solution  causes  coagulation. 

— the  solution  is  precipitated  by  saturation  with  sodic  chloride. 
Carbonic  acid1 — soluble. 

Sodic  carbonate — very  soluble;  solution  not  precipitated  by  carbonic  acid. 
Hydrochloric  acid  (0  4  per  cent.) — very  soluble. 
Me.taphosphoric  acid — insoluble. 
Orlhophosphoric  acid — dissolves. 
Sodic  nu'taphosphate — insoluble. 
Sodic  orthophosphate — very  soluble. 
Potassic  sulphate — very  soluble. 
Calcic  chloride — very  soluble. 
Acetic  acid  (5  per  cent.) — very  soluble. 
Acetic  acid  (glacial) — very  soluble. 
Coagulation  occurs  at  about  64-73°  C. 

Since  this  body  is  precipitated  by  saturation  with  sodic  chloride,  and  dissolves 
with  difficulty  in  a  0.75  per  cent,  solution  of  sodic  chloride,  it  seems  more  akin 
to  myosin  than  other  of  the  globulins. 

The  Copper-venom-globulin. — After  the  separation  of  the  water-venom-glbbulin 
the  filtrate  gives  well-marked  proteid  reactions  and  decided  coagulation  by  boiling. 
If  now  a  few  drops  of  cupric  sulphate  (10  per  cent.)  be  cautiously  added  a  second 
precipitate  will  occur,  and  which  can  be  separated  as  in  the  previous  instance.  In 
adding  the  cupric  sulphate  great  caution  must  be  exercised  lest  too  much  be  added 
with  the  result  of  a  complete  or  partial  re-solution  of  the  precipitate. 

The  precipitate  is  sometimes  comparatively  slight  at  first,  increasing  upon  stand- 
ing, and  complete  within  about  twenty-four  hours.  The  clear  filtrate  should  give 
no  precipitate  after  the  addition  of  a  small  amount  of  the  copper  solution  and  after 
standing  twenty-four  hours  longer. 

1  In  all  of  these  reactions  with  the  globulins,  unless  otherwise  apparent,  about  1  c.  c.  of  the 
suspended  globulin  in  distilled  water  was  placed  in  a  small  test-tube,  and  from  one  to  two  drops  of 
standard  laboratory  solutions  of  reagents  were  allowed  to  run  down  the  inside  of  the  tube. 

We  have  made  a  large  number  of  tests  with  various  reagents,  and  from  this  number  have  selected 
only  such  as  will  serve  us  some  purpose  in  distinguishing  these  different  bodies. 

2  Where  carbonic  acid  is  used  in  these  tests  we  have  reference  to  the  super-saturated  carbonic 
acid  water  (soda  water)  of  commerce. 


12  THE    VENOMS   OF   CERTAIN    THANATOPHIDEJ2. 

The  precipitate  thus  obtained  is  washed  as  in  the  preparation  of  the  water- 
venom-globulin,  and  when  thus  purified  it  does  not  give  any  color  reaction  with  the 
ammonia  or  the  ferrocyanide  and  acetic-acid  tests  for  copper,  and  therefore  cannot 
be  regarded  as  a  salt  of  this  metal. 

The  copper-venom-globulin  gives  the  following  reactions:  — 

Decided  reactions  with  the  usual  proteid  tests. 

Sodic  chloride  (0  75  per  cent.) — insoluble. 
(10       "         )— insoluble. 

— the  addition  of  crystals  of  sodic  chloride  seems  to  dissolve  it 
slightly;  this  solution  is  cleared  somewhat  by  boiling;  the 
same  eifect  by  boiling  the  suspended  mixture;  the  clearing 
is  no  doubt  the  result  of  the  formation  of  coagula. 

Carbonic  acid — insoluble. 

Sodic  carbonate — very  soluble,  forming  a  beautiful  clear  solution ;  boiling  has  no  effect;  the  solu- 
tion is  precipitated  by  carbonic  acid. 

Hydrochloric  acid  (0.4  per  cent.) — exceedingly  soluble. 

Metaphosphoric  acid — insoluble  ;  boiling  no  effect. 

Orthophosphoric  acid — very  soluble,  forming  an  absolutely  clear  solution;  boiling  has  no  decided 

effect. 

Sodic  metaphospliate — insoluble  ;  boiling  no  effect. 

Sodic  orthophosphate — soluble  in  a  much  larger  amount  than  is  necessary  in  dissolving  the  water- 
venom-globulin  ;  boiling  has  no  effect,  unless  to  clear  the 
solution  some. 

Poiassic  sulphate — insoluble ;  boiling  no  effect. 

Calcic  chloride — less  soluble  than  waier-venom-globulin. 

Acetic  acid  (5  per  cent.) — very  soluble. 

Acetic  acid  (glacial) — very  soluble. 

The  Dialysis-venom-globulin. — The  filtrate,  after  the  separation  of  the  watcr- 
venom-globulin  and  copper-venom-globulin,  still  gives  a  decided  amount  of  coagula 
by  boiling,  and  also  all  of  the  characteristic  color  reactions  for  proteids.  If  the 
filtrate  be  now  subjected  to  dialysis,  best  by  means  of  a  large  dialyser  placed  over 
running  water,  in  the  course  of  twenty-four  hours  a  considerable  amount  of  pre- 
cipitate will  be  deposited  within  the  dialyser,  and  which  may  be  collected  on  a 
filter,  and  repeatedly  washed  as  in  the  preparation  of  the  preceding  globulins. 

If  dialysis  is  carried  on  for  a  sufficient  length  of  time  the  whole  of  this  principle 
will  be  precipitated,  since  the  filtrate  from  the  globulin  will  give  no  coagula  by 
boiling,  nor  any  precipitate  by  strong  nitric  acid.  A  proteid  still  remains  in  solu- 
tion, however,  which  has  been  already  alluded  to  as  being  a  peptone.  This  body 
being  less  dialysable  than  the  salts  which  hold  the  globulins  in  solution,  still  remains 
in  part  within  the  dialyser,  even  when  the  salts  are  so  fully  withdrawn  as  to  entirely 
precipitate  the  globulins. 

The  dialysis-venom-globulin  gives  the  following  reactions:  — 

Decided  reactions  with  the  usual  proteid  tests. 
Sodic  chloride  (0.75  per  cent.) — insoluble. 

(10       "         )— slightly  soluble. 

(crystals') — more  soluble,  forming  a  very  cloudy  solution  ;  boiling  clears  the 
solution  some;  the  same  degree  of  clearing  does  not  occur  in 
the  mixture  without  the  sodic  chloride. 

— the  addition  of  carbonic  acid  to  the  solution  with  crystals  causes 
a  beautiful  clear  solution,  which  is  made  cloudy  by  boiling. 


THE  CHEMISTRY  OF  VENOMS.  13 

Carbonic  acid — soluble ;  cloudiness  by  boiling. 

Sodic  carbonate — very  soluble  ;  boiling  no  effect. 

Hydrochloric  acid  (0.4  per  cent.) — very  soluble. 

Metaphosphoric  acid — rendered  of  a  yellowish  tint;  not  appreciably  dissolved  ;  boiling  no  appre- 
ciable effect. 

Orthophosphoric  acid — very  soluble;  boiling  no  effect. 

,SW/c  metaphogphate — very  soluble,  forming  a  very  clear  solution;  boiling  no  effect. 

Sodic  orthophosphale — slightly  soluble;  dissolving  slowly  in  excess,  forming  a  slightly  turbid 

solution  ;  boiling  clears  absolutely. 

Potassic  sulphate — insoluble  ;  boiling  no  decided  effect. 

Calcic  chloride — soluble  by  the  addition  of  a  comparatively  larger  amount ;  boiling  causes 

coagulation. 

Acetic  acid  (5  per  cent.) — very  soluble. 

Acetic  acid  (glacial) — very  soluble. 

The  Venom  Peptone. — After  the  separation  of  the  dialysis-globulin  the  filtrate,  as 
before  stated,  gives  no  coagula  by  brief  boiling,  but  by  testing  with  the  usual  proteid 
tests  very  decided  reactions  are  obtained.  It  is  further  found  that  if  the  above 
filtrate  is  placed  in  a  fresh  dialyser,  that  the  principle  giving  the  proteid  reactions 
will  readily  pass  through  the  membrane.  The  fact  that  this  substance  will  dialyse 
readily,  and  that  it  is  not  immediately  coagulated  at  the  temperature  of  boiling 
water,  and  not  precipitated  by  cupric  sulphate  and  ferric  chloride,  nor  by  neutrali- 
zation, renders  it  certain  that  it  belongs  to  a  peculiar  class  of  bodies  which  are 
known  as  peptones,  and  which  are  ordinarily  the  result  of  peptic  or  tryptic 
digestion.  This  peptone  may  also  be  prepared  by  briefly  boiling  the  solution  of 
venom,  which  coagulates  the  other  albuminous  principles,  and  leaves  this  in  solu- 
tion; but  the  coagula  caused  by  boiling  the  solution  of  Crotalus  are  so  extremely 
fine,  that  it  is  impossible  to  filter  the  mixture  clear,  even  by  repeated  filtration 
through  many  thicknesses  (7)  of  the  best  filter  paper ;  furthermore,  continued  boil- 
ing causes  a  breaking  down  of  the  peptone  with  the  apparent  formation  of  fine 
coagula  (see  Cobra  peptone,  p.  17).  We,  however,  prepared  the  peptone  by 
dialysis,  and  obtained  the  following  reactions : — 

No  immediate  coagulation  at  a  temperature  of  100°  C. 

Full  reactions  with  the  proteid  color  tests. 

No  precipitate  with  weak  or  strong  iiitric  acid. 

Ferric  chloride. — no  precipitate. 

Cupric  sulphate — no  precipitate. 

Mercuric  chloride — decided  precipitate. 

Absolute  alcohol — precipitate ;  precipitate  redissolvcd  by  the  addition  of  water. 

Mercuric  nitrate — deoided  precipitate. 

Potassic  hydrate — precipitate  by  saturation  ;  precipitate  redissolved  by  the  addition  of  nitric  acid, 

forming  a  decidedly  yellowish  solution,  which  becomes  decolorized  by  further 

addition  of  acid. 
Potassic  ferrocyanide  in  jiYesence  of  weak  acetic  acid — a  precipitate. 

To  revert  now  to  the  globulins  and  their  distinctive  features,  it  seems  clear  that 
these  principles  must  exist  in  the  venom  as  distinct  bodies,  and  are  not  simply 
representatives  of  a  single  globulin  which  have  arisen  through  our  manipulations. 
The  first  distinguishing  feature  between  them  is  represented  in  the  process  of 
isolation,  but  if  we  place  the  reactions  of  the  different  globulins  in  parallel  columns, 


14 


THE  VENOMS  OF  CERTAIN  TH  A  N  A  T  0  P  U  I  D  E 


we  find  that,  while  they  have  very  close  resemblances,  as  they  naturally  should  since 
they  are  so  intimately  related,  they  are  very  readily  distinguished  from  each  other. 
The  properties  of  all  globulins  are  so  readily  affected  by  even  the  simplest  manipu- 
lations that  it  is  likely  that  mere  precipitation  may  affect  them  in  regard  to  their 
solubility,  while  drying  may  completely  destroy  this  property.  Having  these  facts 
in  mind,  it  seems  almost  a  necessity  that  the  processes  through  which  we  put  these 
globulins,  in  order  to  get  them  isolated  in  a  pure  state,  has  more  or  less  modified 
their  chemical,  and  possibly  their  physiological  properties. 

The  tests  made  with  these  globulins  were  all  made  at  different  times,  the  one 
globulin  was  examined  one  day,  and  another  on  another  day,  so  that  the  reactions 
given  are  not  absolutely  accurate  as  a  matter  of  comparison,  but  only  relative,  since 
the  standard  of  solubility,  which  was  of  course  an  arbitrary  one,  was  simply  carried 
in  the  mind  throughout  the  examinations.  We  believe,  however,  that  they  are 
practically  correct. 


Reagent. 

Water-  venom-globulin  . 

Copper-venom-globulin. 

Dialysis-  venom-globulin. 

Sodic  chloride  (10  p.  c.) 

Soluble 

Insoluble 

Slightly  soluble. 

Carbonic  acid 

Soluble 

Insoluble 

Soluble. 

Sodic  carbonate 

(Very  soluble;  not 
^precipitated  by  C02 

Very  soluble  ;  pre-) 
cipitated  by  CO2    ) 

Very  soluble. 

Hydrochloric  acid  (0.4  p.  c.) 

Very  soluble 

Very  soluble 

Very  soluble. 

Metaphosphoric  acid 

Insoluble 

Insoluble 

(Insoluble;  rendered 
^of  a  yellowish  tint. 

Orthophosphoric  acid 

Soluble 

Very  soluble 

Very  soluble. 

Sodic  metaphosphate 

Insoluble 

Insoluble 

Very  soluble. 

Sodic  orthophosphate 

Very  soluble 

Less  soluble 

Still  less  soluble. 

Potassic  sulphate 

Very  soluble 

Insoluble 

Insoluble. 

Calcic  chloride 

Very  soluble 

Less  soluble 

Less  soluble. 

Acetic  acid  (5  per  cent.) 

Very  soluble 

Soluble 

Very  soluble. 

Acetic  acid  (glacial) 

Very  soluble 

Soluble 

Very  soluble. 

The  venom  of  the  Moccasin  (Ancistrodon  piscivorus)  was  subjected  to  an  analysis 
similar  to  that  of  the  Crotalus,  the  isolated  proteids  giving  the  following  reactions: — 

Water-venom-globiilin. 

Decided  reactions  with  the  usual  proteid  color  tests. 

Boiling — clears  the  mixture  without  the  apparent  formation  of  any  coagula. 
Sodic  chloride  (0.75  per  cent.) — insoluble. 

(10       "         ) — somewhat  soluble,  solution  not  absolutely  clear;  boiling  clears 

absolutely  without  the  formation  of  coagula 

(crystals) — somewhat  soluble ;  solution  not  precipitated  by  carbonic  acid. 
Carbonic  add — insoluble. 
Sodic  carbonate — soluble,  forming  slightly  turbid   solution;   boiling  clears  the  solution  without 

giving  coagula;  the  addition  of  crystals  of  sodic  chloride  to 

the  hot  boiled  solution  causes  a  precipitate,  this  precipitate 

being  coagulated  by  boiling. 
Hydrochloric  acid  (0.4  per  cent.) — somewhat  soluble. 

(5       "         )_soluble. 
Metaphosphoric  acid — in  sol  ubl  e . 
Orthophosphoric  acid — soluble. 

Sodic  metaphosphate — slightly  soluble;  solution  rendered  clearer  by  boiling. 
Sodic  orthophosphate — soluble;  solution  rendered  absolutely  clear  by  boiling. 


THE  CHEMISTRY  OF  VENOMS.  15 

Potassic  sulphate — soluble  ;  solution  rendered  absolutely  clear  by  boiling. 
Calcic  chloride — soluble;  solution  rendered  clearer  by  boiling. 
Acetic  acid  (5  per  cent.) — insoluble. 
Acetic  acid  (glacial) — insoluble  ? 

Copper-venom-rjlobulin. 

Boiling — clears  somewhat;  no  coagula. 
Sodic  chloride  (0.75  per  cent.) — insoluble. 
(10        "         )— insoluble. 

(crystals) — insoluble;  boiling  partially  clears  without  the  formation  of  any 

coagula. 

Carbonic  acid — somewhat  soluble;  boiling  clears  absolutely. 
Sodic  carbonate — very  soluble  ;  boiling  no  effect. 
Hydrochloric  acid  (0.4  per  cent.) — very  soluble. 
Metaphosphoric  acid — insoluble;  boiling  appears  to  clear  slightly. 
Orthophosphoric  acid — very  soluble. 

Sodic  metaphosphate — insoluble;  boiling  clears  somewhat. 
Sodic  orthophosphate — somewhat  soluble;  boiling  clears  beautifully. 
Potassic  sulphate — insoluble  ;  boiling  clears  slightly. 
Calcic  chloride — slowly  dissolved;    not   so    soluble   as   water-globulin;   boiling  gives   a   slight 

cloudiness. 

Acetic  acid  (5  per  cent.) — soluble. 
Acetic  acid  (glacial) — soluble. 

Dialysis-venom-globulin. 

Boiling — clears  almost  absolutely  without  the  apparent  formation  of  coagula;   boiled  solution 

precipitated  by  saturation  with  crystals  of  sodic  chloride. 
Sodic  chloride  (0.75  per  cent.) — insoluble. 

(10       "        ) — somewhat  soluble;   dissolves  slowly,  forming  a  slightly  turbid 

solution ;   boiling  seems  to  clear  some  without  the  formation 

of  coagula. 

Carbonic  acid — very  soluble  ;  slight  turbidity  by  boiling. 
Sodic  carbonate — very  soluble;  boiling  no  effect. 
Hydrochloric  acid  (0.4  per  cent.) — very  soluble. 
Metaphosphoric  acid — slightly  soluble  ;  yellowish  tint ;  boiling  clears  slightly  with  the  formation 

of  coagula. 

Orthophosphoric  acid — very  soluble  ;  boiling  no  effect. 
Sodic  metaphosphate — insoluble. 
Sodic  orthophosphate — soluble  ;  boiling  no  effect. 
Potassic  sulphate — somewhat  soluble. 

Calcic  chloride — very  soluble,  form  a  beautiful  clear  solution;  boiling  causes  slight  turbidity. 
Acetic  acid  (5  per  cent.) — soluble 
Acetic  acid  (glacial) — soluble 

Moccasin  Peptone. 

1.  Readily  dialysable. 

2.  Not  immediately  coagulated  at  a  temperature  of  100°  C.,  but  gradually  coagulated  by  pro- 
longed boiling  (see  Cobra  peptone,  p.  17). 

3.  Reaction  with  the  xantho-proteic  test  (nitric  acid  and  ammonia) 

4.  Reaction  with  Millon's  reagent  (mercuric  nitrate) 

5.  No  precipitate  with  weak  or  strong  nitric  acid. 

6.  No  precipitate  with  C02. 

7.  No  precipitate  with  ferric  chloride. 

8.  No  precipitate  with  cupric  sulphate. 


16 


THE    VENOMS   OF    CERTAIN    THANATOPHIDEJB. 


9.   Precipitated  by  mercuric  chloride. 

10.  Precipitated  by  absolute  alcohol. 

11.  Gives  a  faiut  reddish  tinge  with  a  strong  solution  of  potassium  hydrate,  and  a  trace  of  cupric 
sulphate. 

12.  Not  precipitated  by  strong  acetic  acid  (glacial). 

13.  Precipitated  by  very  dilute  acetic  acid ;  precipitate  being  rcdissolved  by  further  addition  of  acid. 
14    Full  reaction  with  Adamkiewicz's  test  for  proteids. 

15.  Precipitated  by  adding  a  large  quantity  of  sodium  chloride,  the  precipitate  being  redissolved 
on  the  addition  of  a  large  quantity  of  glacial  acetic  acid. 

16.  Precipitated  by  mercuric  nitrate. 

17.  Precipitated  by  absolute  alcohol ;  precipitate  being  apparently  redissolved  on  the  addition  of 
water. 

18.  Precipitated  by  saturation  with  potassium  hydrate;  precipitate  being  redissolved  by  the  addi- 
tion of  nitric  acid,  with  the  formation  of  a  decidedly  yellow  solution  (xantho-proteic)  which  becomes 
decolorized  by  addition  of  acid. 

19.  Precipitated  by  potassium  ferrocyanide  in  the  presence  of  weak  acetic  acid. 

Venom-peptone  by  dialysis  gives  identical  reactions. 

For  convenience  of  comparison  we  append  here  in  parallel  columns  the  principal 
reactions  of  the  Moccasin  globulins,  remembering  in  this  connection  the  difference 
in  the  properties  manifest  in  their  methods  of  preparation. 


Reagent. 

Water-  venom-globulin. 

Copper-venom-gl  obul  i  n  . 

Dialysis-venom-globulin. 

Boiling 

(  Clears  almost  abso- 
|     lately 

Clears  some 

Clears  some. 

Sodic  chloride  (10  per  cent.) 

Somewhat  soluble 

Insoluble 

Somewhat  soluble. 

Carbonic  acid 

Insoluble 

Somewhat  soluble 

Very  soluble. 

Sodic  carbonate 

Soluble 

Very  soluble 

Very  soluble. 

Hydrochloric  acid  (0.4  p.  c.) 

Somewhat  soluble 

Very  soluble 

Very  soluble. 

Metaphosphoric  acid 

Insoluble 

Insoluble 

Slightly  soluble. 

Orlhophosphoric  acid 

Soluble 

Very  soluble 

Very  soluble. 

Sodic  metaphosphate 

Somewhat  soluble 

Insoluble 

Insoluble. 

Sodic  orthophosphate 

Soluble 

Less  soluble 

Soluble. 

Potassic  sulphate 

Soluble 

Insoluble 

Slightly  soluble 

Calcic  chloride 

Soluble 

Insoluble 

Very  soluble. 

Acetic  acid  (5  per  cent.) 

Insoluble 

Soluble 

Soluble. 

Acetic  acid  (strong) 

Insoluble 

Soluble 

Soluble. 

For  reactions  of  the  peptones  of  the  various  venoms  see  p.  19. 

Cobra  Venom. — We  have  been  able  to  isolate  in  Cobra  venom  only  two  proteids, 
and  these  correspond  in  their  characters  to  the  two  types  of  proteids  found  in 
the  venoms  of  the  Crotalus  and  Ancistrodon.  In  other  words,  we  have  isolated  a 
globulin  and  a  peptone-like  principle.  The  globulin  we  are  able  to  precipitate 
completely  by  the  addition  of  a  proper  amount  of  distilled  water,  after  which  the 
solution  gives  no  coagulum  by  boiling.  There  is  then  left  in  solution  a  proteid, 
which  evidently  belongs  to  the  peptones,  although  giving  some  extraordinary 
reactions. 

The  venom-globulin  thus  isolated  and  purified,  as  in  the  preparation  of  the 
globulins  previously  mentioned,  possesses  the  peculiar  properties  of  the  globulin 
family,  and,  in  accordance  with  our  nomenclature,  since  it  is  entirely  precipitated 
by  the  addition  of  distilled  water,  is  a  water-venom-ylobulin. 


THE  CHEMISTRY  OF  VENOMS.  17 

The  following  are  some  -of  the  reactions  given  by  this  substance  (the  water-venom- 
ylobulin  suspended  in  distilled  water): — 

Jloiliny — coagulates. 

Sodic  chloride  (0.75  per  cent.) — insoluble. 

(10        "         ) — soluble;  boiling  gives  slight  turbidity. 

— sodic  chloride  solution  apparently  unaffected  by  carbonic  acid. 
Carbonic  acid — insoluble. 

Sodic  carbonate — soluble,  slightly  turbid  solution;  boiling  makes  perfectly  clear. 
Hydrochloric  acid  (0.4  per  cent.) — soluble. 
Mela  phosphoric  acid — insoluble;  boiling  no  appreciable  effect. 
Orthophosphoric  acid — very  soluble;  boiling  makes  solution  absolutely  clear. 
Sodic  metaphosphate — insoluble;  boiling  no  appreciable  effect. 
Sodic  orthophosphale — somewhat  soluble;  boiling  renders  perfectly  clear. 
Potassic  sulphate — somewhat  soluble. 

Calcic  chloride — soluble ;  opalescence  of  solution  increased  by  boiling. 
Acetic  acid  (5  per  cent.) — soluble. 
Acetic  acid  (glacial) — soluble. 

Cobra-venom-peptone. — The  venom-peptone  from  Cobra  may  be  prepared  by 
boiling,  thus  coagulating  the  globulin,  or  by  dialysis.  Great  difficulty  is  expe- 
rienced in  the  former  process,  since  the  coagula  are  so  fine  that  it  is  impossible, 
save  in  rare  instances,  to  obtain  a  clear  nitrate,  and  as  to  these  we  have  no  explana- 
tion to  offer  for  the  exception.  The  peptone  prepared  by  boiling  or  by  dialysis 
gives  identical  reactions. 

Before  detailing  the  reactions  of  this  body  it  may  be  well  to  notice  a  peculiar 
property  exhibited  by  all  venom-peptones  which  gives  them  a  very  distinguishing 
feature.  After  boiling  the  venom  for  a  few  minutes  and  then  filtering,  the  filtrate 
will  again  give  further  coagula  by  continued  boiling,  and  so  the  process  of  boiling 
and  filtering,  and  rebelling  the  filtrate  may  go  on  repeatedly,  yet  the  clear  filtrate 
will  in  every  instance  give  fresh  coagula.  Indeed  the  boiling  process  may  be  con- 
tinued for  an  hour  or  more,  and  yet  at  the  end  of  that  time  the  filtrate  will  still 
yield  coagula.  However,  after  the  venom  solution  has  once  been  boiled,  coagula- 
tion does  not  recommence  in  the  filtrate  until  it  has  been  boiled  for  a  few  moments. 
These  most  interesting  facts  suggest  that  the  coagula  formed  after  the  first  boiling 
are  due  to  a  gradual  decomposition  of  what  is  in  some  sense  a  non-coagulable  pro- 
teid,  since  coagulable  proteids  all  coagulate  at  once  and  completely  when  a  definite 
temperature  is  reached ;  the  coagula  which  follow  repeated  or  prolonged  boiling 
appear  to  be  due  to  such  a  decomposition  of  proteids  as  violent  chemical  or  physi- 
cal action  could  alone  account  for. 

It  seems  to  us  perfectly  clear  that  the  body  which  is  thus  gradually  broken  up 
by  prolonged  boiling  is  &  peptone.  Our  principal  reasons  for  this  belief  are  that 
the  body  so  coagulated  is  very  readily  dialysable,  is  not  precipitated  by  ferric 
chloride,  or  cupric  sulphate,  and  in  the  case  of  the  Cobra  is  not  precipitated  by  abso- 
lute alcohol,  or  mercuric  chloride,  is  not  coagulated  below  the  boiling  point,  and  in 
fact  not  until  boiling  has  gone  on  for  a  few  moments.  The  following  reactions 
seem  to  be  sufficiently  characteristic. 

These  results  we  obtained  from  a  solution  of  the  Cobra-venom-peptone  obtained 

3       April,  1888. 


18 


THE    VENOMS    OF    CERTAIN    T  H  A  N  A  T  0  P  H  I  D  E 


by  dialysing  venom  for  forty-eight  hours.     The  dialysate  was  perfectly  clear  and 
neutral  in  reaction:  — 

Boiling — no  result  until  after  a  few  moments,  when  it  becomes  cloudy,  the  cloudiness  increasing 

as  boiling  continues ;  strong  nitric  acid  dissolves  the  precipitate. 

Color  reactions  for  proteidt- — the  xantho-proteic,  Millon  and  Biuret  reactions  are  all  obtained. 
Ferric  chloride — no  effect. 
Cupric  sulphate — no  effect. 
Mercuric  chloride — no  effect. 
Mercuric  nitrate — decided  precipitate. 
Absolute  alcohol — no  precipitate. 

Potassic  ferrocyanide  -(-  weak  acetic  acid — precipitate. 
Nitric  acid  (strong) — no  precipitate. 
Hydrochloric  acid  (strong) — no  precipitate. 
Acetic  acid  (strong) — no  precipitate. 

Sodic  chloride  (saturation) — precipitate;  acetic  acid,  large  quantity,  dissolves. 
Potassic  hydrate  to  saturation — precipitate. 
Tannic  acid — decided  precipitate. 
Basic  acetate  of  lead — decided  precipitate. 

Several  very  remarkable  facts  are  the  coagulation  by  prolonged  boiling  and  the 
non-precipitation  by  mercuric  chloride  and  absolute  alcohol.  Since  this  peptone 
is  precipitated  by  weak  acetic  acid  in  the  presence  of  potassic  ferrocyanide  it  has 
a  slight  resemblance  to  Meissner's  A  peptone,  although  materially  differing,  as 
some  of  the  above  reactions  show,  from  any  other  described  body  of  this  class. 

As  a  matter  of  some  interest,  it  is  desirable  to  know  if  similar  globulins  in 
different  venoms  are  identical  in  their  chemical  nature,  or  whether  they  give  any 
reactions  which  may  distinguish  them.  We  have  accordingly,  as  in  previous  cases, 
placed  the  reactions  of  the  corresponding  globulins  side  by  side. 

I.   Water-venom-globulin. 


Reagent. 

Crotalus  horridus. 

Ancistrodon  piscivoris. 

Cobra. 

Boiling 

Coagulates 

Apparently  dissolves 

Coagulates. 

Sodic  chloride  (10  per  cent.) 

Soluble 

Somewhat  soluble 

Soluble. 

Carbonic  acid 

Soluble 

Insoluble 

Insoluble. 

Sodic  carbonate 

Soluble 

Soluble 

Soluble. 

Hydrochloric  acid  (0.4  p.  c.) 

Soluble 

Somewhat  soluble 

Soluble. 

Melaphosphoric  acid 

Insoluble 

Insoluble 

Insoluble. 

Orthophosphoric  acid 

Soluble 

Soluble 

Soluble. 

Sodic  metaphosphale 

Insoluble 

Somewhat  soluble 

Insoluble. 

Sodic  orthophosphate 

Very  soluble 

Soluble 

Somewhat  soluble. 

Potassic  sulphate 

Very  soluble 

Soluble 

Somewhat  soluble. 

Calcic  chloride 

Very  soluble 

Soluble 

Soluble. 

Acetic  acid  (5  per  cent.) 

Soluble 

Insoluble 

Soluble. 

Acetic  acid  (strong) 

Soluble 

Insoluble 

Soluble. 

THE    CHEMIST  11  Y    OF    VENOMS. 
II.    Copper-venom-ylolndin. 


19 


Reagent. 

Crotalus  horridus. 

Aneistrodon  piscivorus. 

Boiling 

Coagulates 

Apparently  dissolves. 

Sodic  chloride  (10  per  cent.) 

Insoluble 

Insoluble. 

Carbonic  acid 

Insoluble 

Somewhat  soluble. 

Sodic  carbonate 

Very  soluble 

Very  soluble. 

Hydrochloric  acid  (0.4  p.  e.) 

Very  soluble 

Very  soluble. 

Mataphoxphoric  acid 

Insoluble 

Insoluble. 

Orlh  oph  ouph  oric  acid 

Very  soluble 

Very  soluble. 

Sodic  metaphoephale 

Insoluble 

Insoluble. 

Sodic  orlhophoxphate 

Soluble 

Soluble. 

Potastsic  sulphate 

Insoluble 

Insoluble. 

Calcic  chloride 

Soluble 

Insoluble. 

Acetic  acid  (5  per  cent.) 

Soluble 

Soluble. 

Acetic  acid  (glacial) 

Soluble 

Soluble. 

III.  Diali/sis-venom-f/lobulin. 


Reagent. 

Crotalus  adanianU  us. 

Aneistrodon  piscivorus. 

Boiling 

Coagulation 

No  coagulation  ? 

Sodic  chloride  (10  per  cent.) 

Somewhat  soluble 

Somewhat  soluble. 

Carbonic  acid 

Soluble 

Very  soluble. 

Sodic  carbonate 

Very  soluble 

Very  soluble. 

Hydrochloric  acid  (0.4  p.  c.) 

Very  soluble 

Very  soluble. 

Mela  phosphoric  acid 

Insoluble 

Slightly  soluble. 

Orthophosphoric  acid 

Very  soluble 

Very  soluble. 

Sodic  metaphosphate 

Very  soluble 

Insoluble. 

Sodic  orthophosphale 

Soluble 

Soluble. 

Potassic  sulphate 

Insoluble 

Slightly  soluble. 

Calcic  chloride 

Soluble 

Very  soluble. 

Acetic  acid  (5  per  cent.) 

Soluble 

Soluble. 

Acetic  acid  (glacial) 

Soluble 

Soluble. 

It  will  be  noticed  by  a  careful  comparison  that  the  corresponding  principles  in 
different  venoms  differ  quite  as  much  from  each  other  as  the  globulins  in  any  one 
variety  of  venom. 

Venom  Peptones. — We  have  not  been  able  to  detect  any  chemical  differences 
in  the  venom  peptones  of  the  Crotalus  and  Aneistrodon.  Cobra  venom  peptone 
is  distinguished  from  that  of  the  Crotalus  and  Aneistrodon  by  its  non-precipita- 
bility  by  mercuric  chloride  and  absolute  alcohol. 

Daboia  Venom. — We  have  had  a  small  quantity  (a  few  grains)  of  Daboia  venom 
at  our  disposal,  but  too  little  to  attempt  any  detailed  chemical  investigations.  In 
two  examinations,  however,  with  very  small  quantities,  we  separated  two  bodies 
corresponding  to  those  in  Cobra,  that  is  a  water-venom-globulin  and  a  peptone.  The 
former  exists  in  exceedingly  small  quantity  while  the  latter  dialyses  with  appa- 
rently much  more  difficulty  than  that  of  the  Cobra. 

The  Proportions  of  Proteid  Constituents  in  Different  Venoms. — An  examination 
of  good  specimens  of  the  dried  venoms  of  the  Crotalus  adamanteus,  Aneistrodon 
piscivorus,  and  Cobra  gives  us  the  following  proportions  of  the  globulins  and 
peptones : — 


20  THE   VENOMS   OF   CERTAIN    TH  A  N  A  T  0  P  HI  DE 

Crotalus  adamanteus — 

O.o  grain  dried  venom  =  water-venom-globulin  0.0495 

copper- veil  om-globuliii  0.0375 

dialysis- venom-globulin  0.0360 


0.1 230  =  globulins. 

0.3770  =  peptone'  (estimated.) 

Ancistiodon  piscivorus — 

0.3364  grain  dried  venom  =  water-venom-globulin  0.0034 

copper- venom-globulin  0.0182 

dialysis-venom-globulin  0.0047 


0.0263  =  globulins. 
0.3101  =  peptone1  (estimated). 

According  to  this  estimate  there  would  be  in  0.5  gram  0.0391  globulins. 

0.4609  peptone.' 

Cobra — 

0.2  gram  dried  venom  =  water-venom-globulin      0.0035 

peptone1  0.1965  (estimated). 

According  to  this  estimate  there  would  be  in  0.5  gram  0.0087  globulin. 

0  4912  peptone.1 

From  these  analyses  it  will  be  observed  that  the  dried  venom  of  the  Crotalus 
adamanteus  contains  24.6  per  cent,  of  globulins,  the  Ancistrodon  7.8  per  cent., 
and  the  Cobra  1.75  per  cent.  The  globulins  in  the  Crotalus  venom  appear  to  be 
in  almost  equal  proportions,  while  in  the  Ancistrodon  the  copper-venom-globulin  is 
about  five  times  greater  than  the  water-venom-globulin  and  about  four  times  more 
than  the  dialysis-venom-globulin — the  two  latter  being  nearly  in  the  same  propor- 
tion— therefore  constituting  more  than  half  of  the  entire  weight  of  globulins. 

These  differences  in  the  proportions  of  the  various  globulins  in  any  specimen  of 
venom  and  the  differences  in  the  proportions  of  globulins  and  peptones  in  different 
venoms  are  of  immense  importance  in  affording  an  explanation  of  the  physiological 
peculiarities  exhibited  in  poisoning  by  different  species  of  snakes.  It  will  be 
observed  that  the  proportion  of  globulins  in  Crotalus  is  over  three  times  the 
quantity  in  the  Ancistrodon,  and  nearly  fifteen  times  that  in  the  Cobra. 

1  Including  the  salts,  which  are  in  very  small  quantity. 


EFFECTS  OF  VARIOUS  AGENTS  ON  VENOM.         21 


CHAPTER    III. 
EFFECTS  OF  VARIOUS  AGENTS  ON  VENOM.. 

Effects  of  Various  Agents  on  Venom. — The  influence  of  acids,  alkalies,  and  salts 
on  venoms  has  been  studied  by  several  observers,  with  results  which  vary  remark- 
ably; so  that  for  this  and  for  other  reasons  there  is  still  room  for  research  of  this 
nature.  The  questions  thus  brought  up  have  a  twofold  interest,  the  one  chemical 
and  the  other  toxic.  Numerous  bodies  precipitate  or  dissolve  venoms ;  but  among 
those  which  most  plainly  alter  these  poisons,  only  a  few  .so  change  them  as  to 
lessen  or  destroy  their  poisonous  efficiency.  Unfortunately,  that  which  alters  the 
poison  as  such,  is  always  equally  destructive  to  the  tissues  of  the  body,  and  no 
agent  as  yet  employed  can  be  shown  to  have  the  power  to  enter  the  blood,  and 
there  affect  the  venom  without  doing  harm  to  other  albuminous  substances.  So 
far,  we  have  learned  only  that  amidst  the  agents  which  precipitate  venom,  there 
are  some  which  weaken  or  annihilate  its  toxic  force.  They  can  be  thrown  into 
the  fang  tracks,  and  where  they  are  made  to  mingle  with  the  venom  will  destroy  it 
as  impartially  as  they  do  the  innocent  tissues  in  which  it  lies. 

It  may  not  be  out  of  place  to  remark  that  we  have  made  no  direct  study  of 
agents  as  antidotes.  Too  much  yet  remains  to  be  known  of  these  poisons  before 
we  can  hope  to  find  a  means  of  antagonizing  them  physiologically.  Our  local  or 
chemical  antidotes  are  sufficiently  effective. 

Effect  of  Desiccation  of  Venom. — Allowed  to  dry  at  ordinary  temperatures,  the 
venoms  retain  their  poisonous  activity  almost  unaltered.  When  again  water  is 
added  they  act  as  usual,  except  that,  owing  perhaps  to  imperfections  in  redissolu- 
tion,  they  do  not  produce  as  much  local  effect  within  as  short  a  time  as  do  the 
fresh  fluid  venoms.  Neither,  it  may  be  added,  is  the  general  toxic  influence  quite 
as  rapid  when  venom  has  been  once  desiccated. 

The  Effects  of  Various  Agents  on  the  Toxicity  of  Venoms.  Age. — Some  fresh  venom 
of  the  Crotalus  horridus  was  dissolved  in  an  equal  quantity  of  pure  glycerine  and 
the  vial  corked  and  sealed  in  1863.  In  November,  1882,  the  contents  of  the  vial' 
were  examined.  The  solution  was  perfectly  clear,  and  had  at  the  bottom  a  small 
mass  of  what  appeared  to  be  a  fungous  growth.  Some  of  the  venom  was  now 
injected  into  various  animals  to  test  its  toxicity.  The  following  experiment  attests 
its  power : — 

Experiment.— Pigeon.     Injected,  at  5:12  P.M.,  into  the  muscles  of  the  thigh 
about  six  drops  of  the  above  glycerin  solution. 
5:14.   Animal  decidedly  weakened. 
5:25.   There  is  considerable  blackening  of  the  tissues  about  the  point  of  injection,  the  parts 


22  THE   VENOMS   OF   CERTAIN   THANATOPHIDE^E. 

being  much  swollen,  the  leg  stiff,  the  muscles  at  the  point  of  injection  are  paralyzed,  and 
sensibility  of  the  leg  destroyed.  The  pigeon  lies  on  its  side  unable  to  stand,  is  exceedingly 
prostrated,  and  breathes  laboriously.  Observation  now  ceased  until  8  A.  M.  following  morn- 
ing, when  the  animal  was  found  dead  and  in  general  rigor  mortis,  excepting  the  muscles  at 
point  of  injection. 

Autopsy. — The  tissues  were  dark,  congested,  and  suffused  with  serum  for  an  area  of  one 
and  a  half  inches  from  point  of  injection.  The  viscera  of  the  thoracic  and  abdominal  cavities 
appeared  slightly  congested ;  the  heart  was  arrested  in  systole  and  contained  dark  clots ;  the 
blood  everywhere  was  dark  and  clotted.  Microscopically  the  muscular  fibres  did  not  appear 
to  be  greatly  disorganized,  although  in  some  of  the  fibres  no  transverse  strias  or  nuclei  could 
be  discovered. 

TJie  Effects  of  Dry  Heat.  Experiment. — 0.03  gram  of  dried  (Crotalus  adam- 
anteus)  venom  was  subjected  in  a  dry  oven  to  a  gradually  rising  temperature  to 
83. 5C  C.,  and  maintained  at  this  point  for  half  an  hour.  The  venom,  after  cooling, 
was  dissolved  in  1  c.  c.  of  distilled  water. 

2:57.  Injected  the  above  into  the  thigh  of  a  pigeon. 

4:49.  Violent  convulsions  and  death.     Local  effects  decidedly  marked. 

Experiment. — Repeated  the  above,  but  subjecting  the  venom  to  a  temperature 
of  100  C.  for  ten  minutes. 

3:42.  Injected  into  the  thigh  of  a  pigeon. 

6:00.  No  decided  symptoms.  On  the  following  morning  the  animal  was  dead.  The  local 
effects  were  marked. 

Experiment. — Repeated  the  above,  but  subjecting  the  venom  to  a  temperature 
of  110°  C.  for  thirty  minutes. 

4:46.   Injected  into  the  thigh  of  a  pigeon. 

5:25.   Convulsions. 

5:45.   Died.     The  local  effects  were  marked. 

From  these  results  it  seems  clear  that  heating  the  dry  venom  to  a  degree  above 
boiling  point  does  not  apparently  alter  its  poisonous  activity.  The  delay  in 
the  occurrence  of  death  in  the  second  experiment  suggests  that  the  venom  was 
altered,  but  in  the  third  experiment  in  which  the  temperature  was  even  higher, 
and  this  degree  of  heat  maintained  for  a  much  longer  time,  death  occurred  even 
sooner  than  in  the  first  experiment,  showing  that  the  differences  must  have  been 
dependent  upon  conditions  in  the  animals. 

The  Effects  of  Moist  Heat.  Experiment. —  0.03  gram  dried  venom  (Crotalns 
adamantens)  was  dissolved  in  1  c.  c.  distilled  water,  and  gradually  heated  until  a 
flocculent  precipitate  occurred. 

This  was  injected  into  the  thigh  of  a  pigeon  in  the  evening.  The  next  morning  the  animal 
was  found  dead. 

Experiment. — 0.03  gram  dried  venom  (Crotalus  adamanteiis)  was  dissolved  in 
1  c.  c.  distilled  water  and  subjected  to  a  gradually  rising  temperature  to  50°  C. 

3:49.  Injected  the  above  into  the  breast  muscles  of  a  pigeon. 

3:51.  Very  weak,  pupils  apparently  contracted,  trembling;  breathing  laborious. 

4:00.  Dead.  At  the  point  of  injection  the  tissues  were  decidedly  congested  and  purplish 
and  suffused  with  blood.  The  blood  generally  was  fluid,  but  some  soft  clots  were  found  in  the 
abdominal  vessels. 


EFFECTS    OF    VARIOUS    AGENTS    ON    VENOM.  23 

Experiment. — Subjected  a  similar  amount  of  venom  in  solution  to  a  rising 
temperature  to  65°  C. 

4:01.  Injected  into  the  breast  muscles  of  a  pigeon. 
4:05.   Head  depressed. 
4:10.   Very  weak,  falls  on  the  side. 

5:02.  Dead.  The  local  effect  is  not  so  marked  as  in  the  previous  experiment.  The  injec- 
tion was  merely  subcutaneous.  The  viscera  did  not  appear  congested  or  abnormal;  the  heart 
was  arrested  in  systole;  blood  everywhere  fluid  and  dark;  no  ecehymoses  in  the  peritoneum; 
muscles  appear  darker  than  normal. 

Experiment. — Repeated  the  above,  but  increasing  temperature  to  74°  C. 

4:13.   Injected  into  the  breast  muscles  of  a  pigeon. 

4:19.   Weak,  falls  on  side. 

5:05.  Dead.     Blood  clotted ;  local  effect  the  same  as  in  previous  experiment. 

Experiment. — Results  the  same  as  in  the  last  experiment,  excepting  that  the  local 
effects  were  more  marked.  This  animal  lived  a  half  hour  longer  than  the  last, 
which  will  probably  account  for  the  difference. 

Experiment.— The  same,  but  subjecting  the  solution  to  76.5°  C. 

4:04.   Injected  into  the  breast  muscles  of  a  pigeon. 
4:27.   Unable  to  stand. 
6:00.  Nearly  dead. 

Following  morning.    Extremely  feeble,  too  weak  to  stand;  there  is  a  muco-sanguinolent 
discharge  from  the  bowels. 
Second  day.   Very  feeble. 
Third  day.   Recovering. 

Experiment. — The  same,  but  subjecting  the  solution  to  79.5°  C. 

4:00.   Injected  into  the  breast  muscles  of  a  pigeon. 
5:50.  No  symptoms. 
Following  morning  animal  well. 

Experiment. — The  same,  but  subjecting  the  solution  to  81°  C. 

4:31.   Injected  into  the  breast  muscles  of  a  pigeon. 
4:45.   Apparently  a  little  stupid. 
5:50.   No  further  effect. 
Following  morning.   Animal  well. 
Second  morning.   Animal  well. 

Experiment. — Boiled  a  similar  amount  of  solution  for  two  minutes. 

3:26.   Injected  into  the  breast  muscles  of  a  pigeon. 

4:30.   No  effect. 

Following  morning.   No  effect. 

The  above  very  interesting  series  of  experiments  clearly  shows  that  the  effect 
of  heat  on  a  solution  of  venom  is  very  positive,  that  the  toxicity  of  venom  is 
decidedly  affected,  and  that  the  greater  the  increase  of  temperature  between 
certain  limits  the  greater  is  the  destruction  of  the  poisonous  power  of  the  venom. 
It  will  be  observed  in  the  second  experiment,  which  is  the  first  in  which  any 
positive  temperature  was  observed,  that  the  animal  died  in  about  ten  minutes  after 
injection ;  in  the  third  experiment  in  about  one  hour ;  in  the  fourth  and  fifth 
experiments  in  about  three-fourths  of  an  hour,  and  an  hour  and  three-quarters 
respectively,  in  the  sixth  experiment  in  about  two  hours ;  the  animal  was  nearly 


24  THE    VENOMS    OF    CERTAIN    THANATOPHIDE^E. 

dead,  but  finally  recovered  in  the  seventh  experiment  and  in  the  subsequent  ones 
there  were  no  poisonous  symptoms.  It  will  thus  be  observed  that  there  is  a  gradual 
impairment  of  the  toxicity  of  the  venom  increasing  with  the  increase  of  tempera- 
ture, and  that  when  we  reach  76.5°  C.  we  have  almost  reached  the  temperature  at 
which  toxicity  seems  to  be  completely  destroyed.  We  say  seems  completely 
destroyed,  because  we  have  found  that  the  solution  is  still  toxic  even  when  boiled, 
although  there  is  not  sufficient  active  poisonous  matter  left  after  boiling  in  the 
small  amount  of  venom  we  used  in  this  group  of  observations  to  cause  decidedly 
poisonous  effects  in  pigeons. 

The  results  of  boiling  solutions  of  Moccasin  and  Cobra,  venoms  are  quite  different 
from  the  above,  as  the  following  experiments  clearly  show: — 

Experiment. — Dissolved  0.015  gram  dried  Moccasin  in  1  c.  c.  distilled  water, 
and  gradually  heated  to  78°  C. 

3:40.   Injected  into  the  breast  of  a  pigeon. 
3:50.  Rocking. 

4:45.   Nearly  gone;  some  local  effect. 

Following  morning  the  animal  was  dead.  The  local  effect  (darkening)  was  marked,  but 
not  comparable  to  that  caused  by  the  unboiled  venom. 

Experiment. — Boiled  0.015  gram  dried  Moccasin  (piscivoris)  dissolved  in  1  c.  c. 
distilled  water  for  one  minute. 

3:28.  Injected  the  above  into  the  breast  muscles  of  a  pigeon. 

3:35.   Too  weak  to  stand. 

4:15.   Dead.     There  are  no  local  effects. 

Experiment. — Dissolved  about  1|  minims  of  fresh  Moccasin  venom  in  about  1 
c.  c.  distilled  water,  then  boiled  in  a  test-tube,  filtered  and  injected  one-half  into 
the  breast  muscles  of  a  pigeon  at  4:30. 

4:55.  Very  slight  local  effect;  darkening  and  swelling;  the  animal  is  weak  and  has  respi- 
ratory disturbance. 

Injected  the  other  half. 

5:00.   Rocking;  irregular  breathing ;  somewhat  stupefied. 

5:20.  Eyes  closed;  stupefied;  breathing  irregular. 

Following  morning.  There  was  a  large,  light-colored,  oadematous  swelling  (see  Plate  No.  1) 
within,  which  was  a  cavity  about  an  inch  in  diameter,  full  of  broken-down  tissue,  having  a 
grayish  muddy,  gangrenous  appearance,  and  a  putrefactive  odor,  while  the  surrounding 
muscular  tissues  were  normal  in  appearance. 

It  will  be  observed  in  this  series  of  experiments  with  the  Moccasin  venom  that 
there  is  also  a  very  decided  alteration  in  the  poisonous  properties  of  the  venom. 
But  here  we  find  that  although  the  amount  of  venom  used  was  only  one-half  the 
quantity  employed  in  the  Crotalus  series,  boiling  does  not  destroy  its  ability  to 
kill.  It  will  also  be  noticed  here,  as  in  the  case  of  the  Crotalus,  that  a  sufficient 
degree  of  heat  has  an  obvious  effect  on  the  power  of  the  venom  to  produce  the 
peculiar  lesions  at  the  point  of  injection. 

The  effect  of  heat  upon  solutions  of  Cobra  venom  is  not  so  marked. 

Experiment. — 0.03  gram  dried  Cobra  venom  was  dissolved  in  1  c.  c.  distilled 
water  and  subjected  to  a  temperature  gradually  rising  to  74°  C. 

4:10.   Injected  into  the  breast  muscles  of  a  pigeon. 
4:16.  Unable  to  stand. 
4:20.  Dead. 


EFFECTS    OF   VARIOUS    AGENTS    ON    VENOM.  25 

Experiment. — The  same,  excepting  that  the  temperature  was  raised  to  79.5°  C. 

4:12.   Injected  as  above. 
4:21.  Unable  to  stand. 
4:25.  Dead. 

Experiment. — The  same,  solution  being  brought  to  boiling  point  in  a  test-tube. 
4:45.   Injected  into  the  breast  muscles  of  a  pigeon. 
5:00.  Unable  to  stand. 
5:03.   Convulsions  followed  by  death. 

Experiment. — 0.015  gram  dried  venom  dissolved  in  1  c.  c.  distilled  water  and 
boiled  in  a  test-tube  for  about  two  minutes. 

3:51.   Injected  into  the  breast  muscles  of  a  pigeon. 

4:15.   Unable  to  stand. 

4:22.  Dead.     No  local  effects. 

From  these  experiments  it  appears  that  the  toxicity  of  venom  is  not  impaired  by 
brief  heating  as  high  as  79.5°  C.,  the  time  of  death  being  in  these  experiments 
about  the  same  as  with  the  unheated  solution.  In  the  last  two  experiments  in 
which  the  solution  was  boiled,  the  time  of  death  is  delayed,  especially  so  in  the  last 
experiment,  but  here  it  must  be  observed  that  but  one-half  the  dose  was  used.1 

In  one  experiment  made  on  the  venom  of  the  Copperhead  (Ancistrodon  contor- 
trix)  the  effect  seemed  to  be  in  degree  between  that  of  the  Grot  us  and  Ancistrodon 
piscivorns. 

Experiment. — 0.03  gram  dried  venom  was  dissolved  in  1  c.  c.  distilled  water  and 
boiled  in  a  test-tube  for  two  minutes. 

5:00.  Injected  into  the  breast  muscles  of  a  pigeon. 
5:10.  Unable  to  stand. 
5:20.  Incoordination. 
6:00.  Very  weak. 

Following  morning.  Dead.  There  were  very  slight  local  effects;  the  blood  was  clotted  in 
soft  black  clots;  heart  arrested  in  systole,  auricles  full  of  clots.  The  interior  of  the  thoracic 
cavity  had  a  mucky  brownish  appearance  ;  the  viscera  did  not  appear  congested,  and  there 
were  no  ecchymoses. 

A  similar  dose  of  the  unheated  copperhead  venom  kills  promptly  with  decided 
local  effects.  It  will  thus  be  apparent  that  boiling  decidedly  alters  its  toxic  power. 

The  effect  of  boiling  on  the  venom  of  the  Crotalophorus  is  as  decided  as  on  that 
of  the  Crotalus. 

Experiment. — Two  drops  of  the  fresh  venom  of  the  Crotalopliorus  was  dissolved 
in  1  c.  c.  distilled  water  and  boiled  for  a  moment. 

4:58.  Injected  into  the  breast  muscles  of  a  pigeon. 

6:15.  In  good  condition;  no  symptoms  up  to  this  time,  excepting  a  little  tendency  to 
droop. 

Following  evening.  Animal  normal. 

The  venom  of  the  Coral  snake  (Elaps  fulvius)  is  affected  to  a  less  degree. 

1  Very  prolonged  boiling,  as  has  been  shown  by  Fayrer  and  by  Ward,  lessens  greatly,  and  at 
last  destroys  toxicity  in  cobra  venom.  The  efficient  cobra  peptone  is,  as  we  have  seen,  converted 
into  a  coagulable  albuminoid,  which  is  then  incapable  of  destroying  life. 

4       April,  1886. 


26       THE  VENOMS  OF  CERTAIN  T  II  AN  A  T  0  P  II I  DE^E. 

Experiment. — Boiled  0.015  gram  dried  Coral  venom  dissolved  in  1  c.  c.  distilled 
water. 

Time  of  injection  ? 

5:45.   Very  weak. 

6:00.  Nearly  dead. 

6:10.   Dead.     No  local  effects.     Blood  coagulates  perfectly. 

A  smaller  amount  of  venom  unboiled  kills  in  from  10-15  minutes  with  decided 
local  effects. 

From  the  experiments  with  the  venom  of  the  Crotalus  adamanteua  detailed  above 
it  appears  as  though  the  toxicity  of  the  venom  was  completely  destroyed  by  boiling, 
but  Weir  Mitchell  found  some  years  ago  that  boiling  did  not  destroy  the  poison- 
ousness  of  the  venom  of  the  Crotalus  durissus,  and  further  work  of  our  own  led  us 
to  believe  that  the  want  of  toxicity  of  our  boiled  solutions  was  only  apparent,  and 
that  there  was  accordingly  a  poisonous  principle  still  present,  but  not  in  deadly 
quantities.  We  therefore  made  some  further  observations,  using  larger  amounts  of 
venom. 

Experiment. — Dissolved  three  drops  of  fresh  Crotalus  adamanteus  venom  in  1.5 
c.  c.  distilled  water  and  boiled. 

4:40.   Injected  into  the  breast  muscles  of  a  pigeon. 

6:10.  No  positive  effects. 

Following  morning.   Dead,  no  characteristic  local  effects. 

Experiment. — Dissolved  0.12  gram  venom  (Crotalus  adamanteus')  in  2  c.  c.  dis- 
tilled water  and  boiled  for  two  or  three  minutes. 

4:40.  Injected  the  above  into  two  pigeons,  giving  each  half. 

Death  within  fourteen  hours  in  both  pigeons.  There  was  some  slight  local  effect,  but 
nothing  comparable  to  what  is  observed  in  the  unhcated  venom.  There  were  no  extravasa- 
tions, and  the  blood  was  clotted.  The  stench  from  putrefaction  at  the  points  of  injection 
was  very  great,  and  the  muscles  around  them  presented  a  pale-grayish  color  as  though  they 
had  been  boiled. 

A  like  result  was  obtained  in  the  case  of  another  pigeon  experimented  on  in  the 
same  way. 

From  the  above  series  of  experiments  it  is  perfectly  clear  that  heating  the  dis- 
solved venom  beyond  a  definite  point,  varying  no  doubt  in  different  venoms,  lessens 
its  toxic  power.  Boiling  for  some  minutes  does  not  destroy  the  poisonous  capacity 
of  the  venoms,  but  simply  impairs  this  quality  to  a  varying  degree,  depending  upon 
peculiarities  in  the  toxic  constituents,  as  we  shall  hereafter  have  reason  to  observe. 
Fayrer  and  Wall,  as  already  noted,  found  that  prolonged  boiling  of  solutions  of 
Cobra  venom  completely  destroyed  the  poisonous  activity  of  that  secretion.  We 
accordingly  made  some  similar  experiments  with  solutions  of  the  venom  of  the 
Crotalus  adamanteus  with  analogous  results. 

Experiment. — 0.03  gram  of  the  dried  venom  of  the  Crotalus  adamanteus  was 
dissolved  in  a  little  distilled  water  and  boiled  for  ten  minutes  in  a  water  bath 
After  being  allowed  to  cool  it  was  injected  into  the  breast  of  a  pigeon. 
1:56.  Injection  practised. 
1:57.  Weak. 
2:00.   Convulsions. 

2:37.   Since  last  observation  has  been  lying  on  its  side,  very  weak. 
2:43.  Dead. 


EFFECTS  OF  VARIOUS  AGENTS  ON  VENOM.        27 

In  a  subsequent  experiment  the  solution  of  venom  was  boiled  for  forty  minutes. 
Three  minutes  after  the  injection  the  pigeon  vomited ;  no  other  toxic  symptoms 
were  observed.  In  another  experiment,  in  which  the  venom  was  boiled  for  one 
hour,  no  symptoms  occurred  but  vomiting.  Both  of  these  pigeons  were  watched 
for  three  days,  but  in  neither  of  them  did  any  poisonous  symptoms  ensue. 

The  Effects  of  Alcohol. — When  alcohol  is  added  to  fresh  venom  or  to  an  aqueous 
solution  of  venom  a  copious  white  precipitate  occurs.  The  following  experiments 
were  made  to  determine  if  the  active  principles  were  entirely  precipitated  by  the 
alcohol,  and  if  the  precipitate  was  poisonous. 

Experiment. — Four  drops  of  the  venom  of  the  Crotalus  adamanteus  were  placed 
in  1  c.  c.  absolute  alcohol.  The  precipitate  was  filtered  and  washed  with  an  addi- 
tional amount  of  alcohol,  the  filtrate  then  being  evaporated  spontaneously  to  1  c.  c. 

The  precipitate  was  placed  in  1  c.  c.  distilled  water  and  injected  into  the  breast 
muscles  of  a  pigeon  at  5:11. 

5:17.   Too  weak  to  stand. 

5:21.   Dead.     There  was  very  little  local  effect. 

The  filtrate  was  injected  into  another  pigeon,  as  above,  at  5:22. 
5:26.   Vomits;  no  further  effects. 

From  this  experiment  it  is  obvious  that  the  presence  of  alcohol  does  not  destroy 
toxicity.  Further  observations  were  made  to  learn  the  effect  of  a  more  prolonged 
action,  and  if  the  precipitate  was  soluble  in  water. 

Experiment. — 0.06  gram  of  dried  Crotalus  adamanteus  was  dissolved  in  3  minims 
of  distilled  water  and  this  was  added  to  3  c.  c.  absolute  alcohol  (Squbb's)  causing  a 
dense  precipitate.  The  mixture  was  allowed  to  stand  for  three  days.  It  was  then 
filtered,  the  precipitate  being  several  times  washed  with  the  filtrate  and  finally  with 
fresh  absolute  alcohol. 

The  precipitate  was  finally  washed  from  the  filter  by  distilled  water,  allowed  to 
dry,  then  digested  in  distilled  water  for  twenty-four  hours,  and,  after  being  filtered, 
was  washed  with  distilled  water.  The  filtrate  was  cloudy,  and  on  being  allowed  to 
stand  for  one  and  a  half  hours  cleared  somewhat,  there  being  an  upper  layer  of 
clear  fluid  and  some  sediment. 

One-fourth  of  the  filtrate  was  now  injected  into  the  breast  muscles  of  a  pigeon 
at  4.43. 

4:54.   Unable  to  stand. 

5:10.  Dead.     There  is  exceedingly  little  local  effect.     The  tissues  at  point  of  injection 
are  suffused  with  blood. 
5:45.  Blood  still  fluid. 

To  one-fourth  of  the  filtrate  one  minum  of  acetic  acid  was  added,  which  caused 
the  mixture  to  become  clear. 

4:41.  Injected  into  a  pigeon  as  above. 
4:52.   Rocking. 
4:54.  Down. 

5:58.   Dead.     There  is  absolutely  no  local  effect  and  there  is  no  suffusion  of  blood  in  the 
tissues  as  in  the  previous  experiment. 


28       THE  VENOMS  OF  CERTAIN  T  H  A  N  A  T  0  P  II I  D  E  M. 

To  one-fourth  of  the  filtrate  a  few  crystals  of  sodic  chloride  were  added,  which 
rendered  the  solution  clear. 

4:49.  Injected  as  before. 

4:55.   Rocking. 

4:58.  Down. 

5:57.  Dead.     The  local  effect  is  intense;  great  blackening  and  infiltration  of  fluid  blood. 

It  will  have  been  seen  that  even  after  subjection  for  three  days  to  the  action  of 
absolute  alcohol  the  venom  has  not  lost  its  toxicity.  It  further  appears  that  the 
addition  of  acetic  acid  or  sodic  chloride,  while  rendering  the  undissolved  material 
soluble  delays  the  time  of  death,  and  that  the  local  effects  of  the  poison  are 
destroyed  by  the  acid  and  intensified  by  the  sodic  chloride.  The  action  of  the 
acid  is  probably  due  either  to  a  powerful  local  constricting  action  on  the  tissues  or 
else  to  a  modification  of  the  properties  of  the  poison.  We  can  give  no  reason 
for  the  cause  in  the  delay  of  death  after  the  addition  of  the  sodic  chloride.  As  the 
animal  in  this  observation  lived  longer  than  in  the  first,  the  increased  local  effect 
may  be  in  this  way  partially  accounted  for. 

The  filtrate  becomes  very  turbid  by  boiling,  and  gives  a  decided  precipitate  with 
nitric  acid,  thus  proving  that  the  water  has  actually  dissolved  some  of  the  precipi- 
tate, and  consequently  that  the  toxicity  of  the  filtrate  cannot  depend  merely  upon 
the  undissolved  particles  of  precipitate  carried  through  the  filter. 

It  is  interesting  to  learn  whether  alcohol  dissolves  any  poisonous  element  of  the 
venom.  In  one  of  the  above  experiments  the  only  effect  following  the  injection 
of  the  alcohol  filtrate  was  vomiting,  but  the  objection  may  be  made  that  the  alcohol 
was  in  sufficient  quantity  to  act  as  a  physiological  antidote  to  any  poisonous  ele- 
ment of  the  venom  which  it  might  have  contained.  We  therefore  made  a  further 
test  of  this  matter  by  using  Cobra  venom,  which  is  more  powerful  than  that  of  the 
Crotalus,  and  using  it  in  larger  quantities. 

Experiment. — Dissolved  0.1  gram  Cobra  venom  in  two  drops  of  distilled  water, 
and  digested  in  2.5  c.  c.  absolute  alcohol  for  about  ten  days.  The  mixture  was 
then  filtered,  and  the  filtrate  evaporated  spontaneously  to  f  of  a  c.  c.  This  was 
injected  into  a  pigeon  without  any  effect. 

The  following  observations  with  Cobra  venom  are  of  great  value  as  throwing 
light  upon  the  different  results  obtained  by  various  investigators  in  studying  the 
action  of  alcohol  on  venom.  In  this  series  of  experiments  varying  proportions  of 
water  were  used  to  dissolve  the  venom. 

Experiment. — Dissolved  0.02  gram  dry  Cobra  venom  in  three  drops  of  distilled 
water,  then  added  1  c.  c.  absolute  alcohol  and  filtered. 

(I.)  4:37.  Injected  into  the  breast  of  a  pigeon  the  above  filtrate — no  symptoms. 
(II.)  4:41.   Injected  the  precipitate  in  a  little  water. 
4:50.  Dead. 

Experiment.— Dissolved  0.03  gram  Cobra  in  ten  drops  of  distilled  water  and 
added  1  c.  c.  absolute  alcohol  and  filtered. 

(I.)  5:00.  Injected  the  filtrate  as  above. 
5:30.   Sick. 

5:53.  Unable  to  stand  ;  extremely  feeble. 
5:55.  Dead. 


.EFFECTS    OF    VARIOUS   AGENTS    ON    VENOM.  29 

(II.)  5:05.  Injected  the  precipitate  with  water. 
5:07^.   Dead. 

In  the  first  scries  the  results  are  the  same  as  in  previous  experiments,  but  in  the 
second  series,  where  a  much  larger  quantity  of  water  was  used,  the  filtrate  caused 
death  in  fifty-five  minutes,  thus  proving  that  if  sufficient  water  he  present,  enough 
of  the  poison  is  carried  with  the  filtrate  to  cause  death,  notwithstanding  the  larger 
amount  of  alcohol  present  and  its  attributed  antidotal  action. 

The  Action  of  Absolute  Alcohol  upon  the  Dried  Venom. — If  dried  venom  be 
placed  in  absolute  alcohol  and  the  mixture  allowed  to  stand  for  some  time,  even 
for  months,  it  will  be  found  that  the  venom  undergoes  no  change  in  its  poisonous 
activity,  nor  does  it  appear  that  the  alcohol  dissolves  out  any  of  the  poisonous 
principles,  since  it  is  found  to  be  innocuous  after  injection,  and  does  not  give  any 
reaction  for  proteids. 

The  Effect  of  the  Caustic  Alkalies  on  the  Toxicity  of  Venoms.  Caustic  Potash. — 
When  caustic  potash  is  added  to  a  solution  of  venom  the  latter  becomes  perfectly 
clear.  If  the  quantity  of  salt  added  to  the  solution  is  below  a  definite  limit  no 
decided  alteration  in  the  capacity  to  kill  is  noticed,  but  as  this  quantity  increases 
-obvious  results  are  observed,  first  a  diminution  in  the  activity  of  the  poison,  and 
at  last  a  complete  loss  of  toxicity. 

Experiment. — Dissolved  0.03  gram  dried  Crotalus  adamanteus  venom  in  1  c.  c. 
of  distilled  water  in-  which  was  previously  dissolved  0.0037  gram  potassic  hydrate. 

3;45.  Injected  into  the  breast  of  a  pigeon. 
4:48.  Weak. 

5:00.  Unable  to  walk;   6:00  ditto. 

fi:30.   Dead.     Heart  arrested  in  systole  ;  no  eechyraoses  ;  well-marked  local  effect;  blood 
fluid  at  the  end  of  sixteen  hours. 
Experiment. — The  same  as  above,  using  0.0075  gram  potassic  hydrate. 

3:43.   Injected. 

5:00.  Weak. 

6:00.   Wreaker;  slight  local  effect. 

Following  morning.   Animal  living,  but  weak;  the  local  effect  is  well  marked. 

Experiment. — The  same,  using  0.015  gram  potassic  hydrate. 

3:47.   Injected. 

7:00.   No  symptoms  up  to  this  time. 

7:30.   Sickish. 

Following  morning.   Sickish;  some  slight  local  effect  at  point  of  injection. 

Experiment. — The  same,  using  0.03  gram  potassic  hydrate. 

3:50.   Injected. 

7:00.  No  symptoms  up  to  this  time. 

Following  morning.  No  symptoms  ;  no  local  effects. 

This  experiment  was  repeated  in  two  other  pigeons  with  a  like  result. 

The  last  series  of  experiments  prove  clearly  that  the  addition  of  potassic  hydrate 
to  a  solution  of  venom,  if  in  sufficient  quantity,  produces  a.  decided  effect  on  the 
activity  of  venom,  and  that  if  added  to  the  venom  of  the  Crotalus  adamanteus  in 
a  quantity  equal  to  the  weight  of  the  dried  poison  the  lethal  action  is  entirely 
destroyed.  In  one  experiment  made  with  the  venom  of  the  Crotalus  horridus  the 


30  THE   VENOMS   OF   CERTAIN   T  H  A  N  A  TO  P  II I  D  E  M. 

same  holds  good,  but  our  experiments  with  Cobra  venom  show  that  a  larger  pro- 
portional quantity  is  needed  to  destroy  its  power. . 

Expi'i-'unciit. — Dissolved  0.015  gram  Cobra  venom  in  0.5  c.  c.  distilled  water, 
then  added  an  equal  amount  of  potassic  hydrate. 

4:05.   Injected  into  the  breast  muscles  of  a  pigeon. 

4:22.   Unable  to  stand. 

4:32.   Convulsions. 

4:37.   Dead. 

This  experiment  was  repeated  with  a  similar  result. 

A  larger  proportion  of  the  potassic  hydrate  was  used  in  the  following  observa- 
tions : — 

Experiment. — The  same  as  above,  using  0.03  gram  (double  the  amount)  of 
potassic  hydrate. 

4:51.  Injected  into  the  breast  of  a  pigeon. 
No  effects. 

Repeated  this  experiment  with  a  similar  result. 

In  one  instance,  however,  we  found  that  0.06  gram  potassic  hydrate  did  not 
effectually  counteract  the  poisonous  activity  of  0.015  gram  dried  Cobra. 

It  has  been  suggested  that  the  non-poisonous  action  of  venom  treated  with 
potassic  hydrate  and  injected  hypodermically,  as  in  the  above  experiments,  depends 
upon  an  effect  of  the  potassic  salt  on  the  tissues,  causing  a  considerable  delaj 
in  the  absorption  of  the  poison,  and  this  suggestion  seems  strengthened  by  the 
result  in  a  rabbit  of  an  intravenous  injection  of  0.015  gram  Crotalus  venom 
with  0.06  gram  potassic  hydrate  in  1  c.  c.  distilled  water.  The  animal  became 
very  sick  soon  after  the  injection,  which  was  given  in  the  evening,  and  remained  in 
this  condition  at  the  end  of  an  hour,  when  the  observation  ceased.  The  following 
morning  it  was  found  dead,  with  post-mortem  appearances  of  the  effects  of  venom. 
Also,  in  another  animal,  which  was  given  intravenously  0.015  gram  of  venom  with 
a  similar  amount  of  potassic  hydrate,  death  occurred  as  promptly  as  with  pure 
venom;  in  fact  rather  earlier. 

In  another  set  of  experiments  on  pigeons,  we  carefully  neutralized  the  potassic 
hydrate  before  injecting.  We  used  in  all  of  this  series  sulphuric  acid  as  the 
neutralizing  principle,  so  that  a  harmless  potassic  sulphate  was  formed.  The 
results  of  this  group  of  experiments  also  go  to  show  that  the  potassic  hydrate 
prevents  the  absorption  of  the  venom. 

Experiment. — Dissolved  0.015  gram  dried  venom  of  the  Crotalus  adamanteus 
in  1  c.  c.  distilled  water  and  added  0.015  gram  potassic  hydrate,  then  carefully 
neutralized  with  acetic  acid. 

This  was  injected  into  the  breast  of  a  pigeon,  causing  death  in  sixteen  minutes. 
Experiment. — Dissolved  0.03  gram  dried  Crotalus  adamanteus  venom  in  1  c.  c. 
distilled  water  and  added  0.015  gram  potassic  hydrate,  and  then  neutralized  as  above. 
4:19.   Injected  as  above. 
4:55.  Weak  ;  breathing  rapid. 
6:20.   Much  weaker. 
Following  morning.  Dead.    Decided  local  effect;  blood  fluid  and  dark. 


EFFECTS    OF    VARIOUS    AGENTS    ON    VENOM.  31 

><  rum  n,t. — The  same,  only  using  0.0075  potassic  hydrate. 

4:53.  Injected  as  before. 

5:00  Weak  ;  breathing  deep. 

5:10.  Dying. 

5:lS.  Dead.     Slight  local  effect;   blood  fluid  and  dark. 

The  records  of  the  above  experiments,  which  are  in  accord  with  Wall's,  show 
that  the  results  after  the  addition  of  the  potassic  hydrate  are  not  the  same  as  in  the 
series  where  the  alkali  was  not  neutralized,  thus  proving  that  the  effect  of  the 
action  of  the  added  alkali  does  not  remain  after  the  latter  is  neutralixed. 

In  previous  observations  we  found  that  solutions  of  venom  were  more  or  less 
impaired  by  boiling,  and  that  this  was  particularly  marked  with  the  venom  of 
the  Crotalus  adamanteus,  0.015  gram  being  rendered  completely  innocuous  to 
pigeons.  It  was  afterwards  found  that  no  coagula  were  formed  by  heating  solu- 
tions of  venom  to  which  had  been  added  some  potassic  hydrate,  as  in  the  above 
experiments.  This  led  us  to  study  the  results  of  heating  solutions  of  venom  to 
which  the  potassic  hydrate  was  added  to  learn  if  heat  was  capable  of  destroying 
or  impairing  toxicity  without  the  occurrence  of  coagulation  as  a  necessary  event. 

Experiment. — Dissolved  0.015  gram  of  the  venom  of  the  Crotalus  adamanteus 
in  1  c.  c.  distilled  water  and  added  0.015  gram  potassic  hydrate,  and  subjected  the 
solution,  as  in  previous  experiments,  to  a  gradually  increasing  temperature  up  to 
74°  C.  It  was  then  injected  into  a  pigeon.  At  the  end  of  twenty-four  hours  there 
was  no  effect. 

In  this  experiment  the  temperature  to  which  the  solution  of  venom  was  sub- 
mitted was  below  the  point  at  which  serious  impairment  of  the  poisonous  power 
of  the  venom  occurs,  yet  the  amount  of  potassic  hydrate  was  sufficient  to  destroy 
its  action.  Other  experiments  were  made  in  which  the  quantity  of  potassic 
hydrate  was  not  sufficient  to  effect  this  end.  We  found  in  previous  experiments 
that  0.0037  gram  potassic  hydrate  was  not  sufficient  to  destroy  the  toxicity  of  0.03 
gram  of  Crotalus  adamanteus  venom,  although  the  time  of  the  occurrence  of  death 
was  considerably  delayed. 

We  used  similar  amounts  of  venom  and  alkali  in  the  three  following  experi- 
ments, using  0.5  c.  c.  distilled  water  for  the  solutions. 

Experiment. — Dissolved  0.09  gram  of  Crotalus  adamanteus  venom  in  1.5  c.  c. 
distilled  water  and  added  0.0 11  gram  of  potassic  hydrate.  This  solution  was 
divided  into  three  parts.  One  of  which  was  heated  to  76.5°  C.,  one  to  79.5°  C., 
and  the  other  to  83.5°  C.  Each  of  which  was  injected  into  the  breast  of  a  pigeon 
and  without  any  evil  consequence  following  within  twelve  hours. 

These  results  indicate  that  heat  impairs  the  poisonous  activity  of  venom  under 
the  above  conditions,  even  though  coagulation  does  not  occur.  In  previous  expe- 
riments recorded  it  was  found  that  at  a  temperature  of  79.5°  0.03  gram  of  Crotalus 
adamanteus  venom  was  rendered  non-toxic.  The  explanation  of  the  further 
impairment  of  the  action  of"  the  poison  by  heating  its  solutions  having  potassic 
hydrate  dissolved  in  them  lies  probably  in  the  fact  that  the  potassic  hydrate  is  placed 
by  heat  under  condition  of  greater  activity.  The  non-coagulability  of  solutions 
of  venom  to  which  potassic  hydrate  was  added  is  no  doubt  due  to  the  alteration 


32      THE  VENOMS  OF  CERTAIN  T  H  AN  A  T  OP  H  ID  E  JC. 

of  the  coagulable  proteids  into  alkali-albumins,  and  as  a  moderate  degree  of 
heat  increases  the  rapidity  of  this  change,  it  is  possible  that  the  smaller  amount 
of  alkali  is  as  effective  under  these  conditions  as  the  larger  amounts  under  ordinary 
conditions.  It  is  not  at  all  improbable  that  the  prolonged  action  of  potassium 
hydrate  on  solutions  of  venom  may  convert  all  of  the  globulins  into  alkali-albumins 
and  thus  destroy  their  poisonous  activity. 

Sodic  Hydrate. — The  effect  of  sodic  hydrate  on  solutions  of  the  venoms  of  the 
Crotalm  adamanteus  and  Jtorridua  appears  to  be  the  same  as  that  of  the  potassic 
salt.  In  one  experiment  with  the  Crotulus  adamanteus,  using  equal  quantities 
(0.03  gram)  of  the  dried  venom  and  alkali,  no  poisonous  effects  followed  its  injec- 
tion; and  in  another  experiment  in  which  0.015  gram  of  venom  and  0.007  gram 
sodic  hydrate  were  used  the  animal  was  rendered  somewhat  sick,  but  fully  recovered. 

In  one  experiment  with  the  venom  of  the  Crotalns  horridus,  using  equal  quan- 
tities (0.015  gram)  of  the  venom  and  sodic  hydrate,  no  poisonous  symptoms  followed. 

The  effect  on  solutions  of  dry  Cobra  venom,  as  in  the  case  of  the  potassic  salt, 
is  not  so  marked. 

Experiment. — Dissolved  0.015  gram  dry  Cobra  venom  in  0.5  c.  c.  distilled  water 
and  added  0.015  gram  sodic  hydrate. 

4:08.  Injected  into  the  breast  of  a  pigeon. 
4:15.  Unable  to  stand. 
4:27.  Dead. 

In  two  other  experiments,  using  double  the  quantity  of  sodic  hydrate,  one  animal 
died  in  one  hour,  and  the  other  in  a  little  less  than  three  hours.  Double  amounts 
therefore  decidedly  impair  toxicity.  In  another  experiment,  in  which  four  times 
the  quantity  of  sodic  hydrate  was  used  (0.015  gram  dried  venom  -j-  0.06  gram 
NaHO),  no  poisonous  symptoms  followed.1 

The  Effects  of  Ammonia. — The  dry  venom  of  the  Crotalm  adamanteus,  which 
was  the  only  one  used,  forms  with  aqua  ammonia  a  turbid  solution,  such  as  is 
formed  with  water.  The  effect  on  the  toxicity  of  the  venom  exerted  by  the 
ammonia  is  not  so  marked  as  with  the  potassic  or  sodic  hydrates. 

Experiment. — Dissolved  0.03  gram  dried  venom  in  two  minims  aqua  ammonia 
(20°)  with  1  c.  c.  distilled  water. 

5:29.   Injected  into  the  breast  muscles  of  a  pigeon. 

5:37.   Unable  to  walk. 

5:46.  Convulsions;  death.     The  local  lesions  are  decidedly  lessened  by  the  alkali. 

Experiment. — The  same,  using  six  minims  aqua  ammonia. 
4:14.   Injected  as  above. 

6:00.  No  marked  symptoms  up  to  this  time,  excepting  droopiness.     The  local  effect  is 
slightly  more  marked  than  in  No.  1. 

Following  morning  the  animal  was  dead. 

In  three  other  experiments  in  which  eight  minims  of  aqua  ammonia  were  used 
two  of  the  animals  were  found  dead  the  following  morning  and  one  recovered.  In 

1  See  Shortt.  Wall,  op.  cit.,  p.  133.  On  the  effects  of  alkalies  and  of  permanganates,  see  Vincent 
Richards,  F.R.C.S.  Ed.,  etc.,  op.  cit. 


EFFECTS  OF  VARIOUS  AGENTS  ON  VENOM.        33 

another  experiment  in  which  the  alkali  was  neutralized  by  sulphuric  acid,  death 
did  not  occur  for  four  hours. 

In  the  first  experiment,  in  which  a  very  small  amount  of  ammonia  was  used, 
death  occurred  in  less  than  twenty  minutes;  in  the  next,  in  which  three  times  the 
quantity  of  ammonia  was  used,  death  did  not  ensue  for  some  hours,  while  in  the 
next  three  a  more  positive  effect  was  no  doubt  apparent  in  the  fact  that  one  of  the 
pigeons  recovered.  In  the  last  experiment  death  did  not  occur  for  over  four  hours, 
even  after  neutralization  of  the  alkali,  indicating,  as  in  the  case  of  the  potassic 
hydrate,  that  some  permanent  effect  had  been  exerted  on  the  venom  by  the 
ammonia. 

Potassium  Carbonate. — Two  experiments  made  with  the  venom  of  the  Crotalus 
adamanteus  render  it  probable  that  the  potassic  carbonate  does  not  exert  any 
decided  effect. 

Experiment. — Dissolved  0.015  gram  venom  in  1  c.  c.  distilled  water  and  added 
0.015  gram  potassic  carbonate. 

4:16.  Injected  into  the  breast  of  a  pigeon. 

4:22.   Down. 

4:25.  Dead.     No  appreciable  local  effect. 

Experiment. — Dissolved  0.03  gram  venom  in  1  c.  c.  distilled  water  and  'added 
0.12  gram  potassic  carbonate. 

5:25.  Injected  into,the  breast  muscles  of  a  pigeon. 

6:45.  Down;  observation  now  ceased. 

Following  morning  found  dead  ;   slight  local  effect. 

Nitric  Acid. — The  powerful  destructive  action  exerted  by  this  acid  on  albumi- 
noids suggests  at  once  that  it  would  in  all  likelihood  completely  destroy  the  poison- 
ous properties  of  venom,  yet  it  has  been  asserted  that  such  is  not  the  case.  In  the 
latter  instance  the  result  was  no  doubt  due  to  the  insufficiency  of  acid  used,  as  we 
have  clearly  determined  in  our  experiments. 

Experiment. — Dissolved  0.03  gram  Crotalus  adamanteus  venom  in  0.5  c.  c.  dis- 
tilled water  and  added  2|  minims  C.  P.  nitric  acid,  which  caused  a  considerable 
precipitate. 

3:32.  Injected  the  above  into  the  breast  of  a  pigeon. 
3:33.   Convulsions,  followed  by  death. 

From  this  result  it  seemed  probable  that  not  enough  acid  had  been  added  to 
throw  down  all  of  the  precipitable  proteids.  In  another  experiment  the  acid  was 
added  to  a  solution  of  venom  and  the  mixture  filtered.  The  filtrate  was  now 
tested  with  nitric  acid  and  a  further  precipitate  occurred.  This  process  was 
repeated  until  no  further  precipitate  followed.  The  filtrate  was  set  aside,  and  the 
precipitate  on  the  filter  washed  with  dilute  nitric  acid  and  then  with  water. 

Experiment. — 5:05  injected  into  the  breast  of  a  pigeon  the  above  filtrate,  which 
measured  3  c.  c.  and  contained  1  c.  c.  nitric  acid. 

6:05.  No  symptoms  except  slight  droopiness. 
Following  morning  no  effects  from  venom. 

5       April,  1888. 


34  THE    VENOMS    OF    CERTAIN   THANATOPHIDE^E. 

Experiment. — 5:55  injected  the  precipitate  in  1  c.  c.  dilute  nitric  acid  with  which 
it  had  been  in  contact  for  two  hours. 

6:05.  No  symptoms. 

Following  morning  animal  in  good  condition. 

It  will  thus  be  observed  that  the  acid  has  completely  destroyed  the  toxicity  of 
venom.  We  made  still  another  experiment  in  which  the  venom  was  rubbed  up 
in  a  mortar  and  the  acid  added  to  it,  and  then  diluted  with  water. 

Experiment. — 0.03  gram  dried  Crotalus  venom  was  rubbed  in  a  mortar  until 
powdered,  and  4  gtt.  C.  P.  nitric  acid  added.  This  formed  a  pasty  mass  of  an 
orange-yellow  color.  With  1  c.  c.  distilled  water  it  formed  a  cloudy,  orange- 
yellow  solution. 

The  above  was  injected  into  the  flank  of  a  half-grown  rabbit,  without  any  symp- 
toms of  venom  poisoning  following  within  twelve  hours. 

A  similar  experiment  was  made  with  a  pigeon  with  a  like  result.  The  acid, 
however,  having  been  neutralized  with  sodic  carbonate  before  injection. 

Muriatic  Acid. — This  acid  does  riot  seem  to  exert  so  strong  an  effect.  Only  one 
experiment  was  made. 

Experiment. — 0.015  gram  dried  Crotalus  venom  was  rubbed  in  a  mortar,  and  to 
it  was  added  4  gtt.  C.  P.  muriatic  acid  forming  a  clear  solution.  With  1  c.  c. 
distilled  water  it  made  a  turbid  solution. 

3:44.  Injected  the  above  into  the  breast  muscles  of  a  pigeon. 

5:00.  Very  sick. 

5:50.  Nearly  dead. 

Following  morning  dead ;  no  local  lesions  from  venom. 

Here  the  amount  of  venom  used  was  only  one-half  of  that  employed  in  the  nitric 
acid  experiment.  The  quantity  of  acid  was  the  same,  but  in  this  experiment  a 
pigeon  was  used. 

As  in  the  series  with  nitric  acid,  an  experiment  was  also  made  in  which  the 
dried  venom  was  powdered  in  a  mortar  and  a  few  drops  of  the  pure  acid  used. 
About  1  c.  c.  of  distilled  water  Avas  added,  and  the  mixture  neutralized  with 
sodic  carbonate.  It  was  then  injected  into  the  breast  of  a  pigeon  with  the  result 
of  death  in  twenty-six  minutes.  • 

Sulphuric  Acid. — Repeated  the  above,  using  instead  of  the  muriatic  acid  5  gtt. 
sulphuric  acid.  The  venom  and  acid  formed  a  clear  syrupy  solution  which  became 
milky  by  the  addition  of  the  water. 

3:53.  Injected  as  above. 

5:50.   Sickish. 

Following  morning  dead;  no  local  symptoms  of  venom  poisoning.' 

Dr.  Mitchell  had  observed  that  if  the  acid  was  afterwards  neutralized  the 
action  of  the  venom  was  not  affected.  The  delay  of  death  in  this  experiment 
seems  to  be  due  to  the  action  of  the  non-neutralized  acid.  We,  however,  made 
an  experiment  by  powdering  the  dried  venom  (0.0 1 5  gram)  in  a  mortar,  adding  a  few 
drops  of  the  pure  acid,  diluting  then  with  about  1  c.  c.  distilled  water,  and  neutral- 
izing with  sodic  carbonate.  This  was  injected  into  the  breast  of  a  pigeon. 


EFFECTS    OF    VARIOUS   AGENTS    ON    VENOM.  35 

For  some  time  after  the  injection  the  bird  was  weak,  and  continued  in  a  feeble 
condition  until  eighteen  hours  after  the  injection,  when  death  ensued. 

It  seems  quite  rejnarkable  that  such  a  powerful  acid  as  sulphuric  does  not  com- 
pletely destroy  the  poisonous  properties  of  the  venom,  and  it  is  even  more  curious 
that  pure  muriatic  acid  seems  to  be  without  effect. 

Acetic  Acid.  Experiment . — Dissolved  0.02  dried  venom  (Crotalus  adamanteus) 
in  0.1  c.  c.  distilled  water  and  added  3  minims  of  glacial  acetic  acid. 

4:30.   Injected  into  the  breast  of  a  pigeon. 
4:37.   Incoordination. 
4:41.   Dead. 

Death  occurred  in  this  experiment  in  such  a  short  time  that  it  was  thought  that 
the  acid  itself  might  have  contributed  to  this  end.  We  therefore  made  another 
experiment  in  which  the  acid  was  neutralized. 

Experiment. — Prepared  the  venom  as  before,  only  neutralizing  the  solution  with 
sodic  carbonate. 

4:35.  Injected  into  the  breast  of  a  pigeon. 
5:10.   Pigeon  unable  to  stand. 
5:15.  Dead. 

The  result  of  this  experiment  indicates  that  the  presence  of  the  free  acid  aids 
the  toxic  action  of  venom. 

Hydrobromic  Acid.  Experiment. — Powdered  0.015  gram  dried  Crotalus  ada- 
manteus  venom  in  a  mortar  and  added  5  gtt.  hydrobromic  acid  (sp.  gr.  1.274),  after 
five  minutes  added  0.5  c.  c.  distilled  water.  The  venom  and  acid  formed  a  slightly 
reddish-colored  solution,  which  became  milky  when  diluted  with  water. 

4:25.   Injected  into  the  breast  muscles  of  a  pigeon. 

4^45.   Sickish. 

4:55.  Unable  to  stand.     (Final  result  not  noted,  but  death  most  certainly  followed.) 

We  repeated  the  above  experiment,  using  10  gtt.  of  acid  mixed  with  an  equal 
part  of  water,  before  dissolving  the  venom  in  it. 

2:49.   Injected  as  above. 

3:07.  Rocking. 

3:30.   Dead  ;  local  effects  of  the  venom  apparent. 

Notwithstanding  we  used  double  the  amount  of  acid  in  this  experiment,  it  does 
not  appear  as  though  the  activity  of  the  venom  was  made  to  differ  much  from  that 
noted  in  the  previous  experiment.  Since  the  previous  dilution  of  the  acid  before 
mixing  with  the  venom  might  have  affected  its  action  a  third  experiment  was 
made  in  which  the  same  quantity  of  acid  was  added,  without  dilution,  to  the 
powdered  venom. 

Experiment. — Powdered  0.015  gram  dried  venom  and  added  10  gtt.  hydro- 
bromic acid,  then  1  c.  c.  distilled  water. 

4:20.   Injected  the  above  into  the  breast  muscles  of  a  pigeon. 
5:00.   No  apparent  effect. 
5:10.   Sickish. 
6:00.  Sickish. 
Following  evening.  Well. 


36  THE   VENOMS   OP    CERTAIN   THANATOPHIDE^E. 

This  last  experiment  was  repeated  with  the  modification  of  leaving  the  acid  in 
contact  with  the  venom  for  one-half  hour  before  the  addition  of  the  water.  It  was 
then  injected  as  above  without  any  obvious  effects  following. 

The  destructive  action  of  the  acid  on  the  venom  of  the  Crotalus  horridus  seems 
to  be  the  same  if  we  can  judge  from  the  single  experiment  which  follows. 

Experiment. — Powdered  0.015  gram  dried  venom  and  added  10  gtt.  hydro- 
bromic  acid,  which  formed  a  muddy  solution  with  a  reddish  color. 

5:18.  Injected  into  the  breast  of  a  pigeon  without  any  obvious  effects  within  twenty-four 
hours. 

The  effect  on  the  activity  of  Cobra  venom,  using  similar  quantities  of  venom  and 
acid  is  very  different. 

Experiment. — Repeated  the  above,  only  substituting  Cobra  venom. 

4:48.  Injected  into  the  breast  muscles  of  a  pigeon. 

•"5:18.  Sick;  breathing  difficult. 

5:30.  Breathing  more  difficult;  convulsive  movements;  incoordination. 

5:35.  Dead. 

Tannic  Acid. — The  action  of  tannic  acid  upon  albuminoids  is  so  decided  that  we 
might  confidently  expect,  since  we  find  the  poisonous  elements  in  venoms  to  be 
proteids,  that  the  activity  of  venom  would  be  greatly  diminished  or  entirely 
destroyed  by  it.  In  one  experiment  made  with  the  venom  of  the  Crotalus  ada- 
manleus  we  found-  comparatively  little  effect. 

Experiment. — Dissolved  0.03  gram  dried  venom  in  a  little  distilled  water  and 
added  1.5  c.  c.  saturated  solution  of  tannic  acid. 

3:35.  Injected  into  the  breast  muscles  of  a  pigeon. 

4:00.   Droopy. 

4:45.  The  same.     Following  morning  dead. 

It,will  be  observed  that  there  is  a  great  delay  in  the  action  of  the  venom,  possi- 
bly due  to  the  powerful  local  constrictive  action  of  the  tannic  acid  on  the  tissues, 
and  possibly,  also,  to  a  direct  action  of  the  acid  on  the  venom  itself.  As  death 
may  have  resulted  from  the  tannic  acid  we  made  a  control  experiment  in  which 
1.5  c.  c.  saturated  solution  was  injected  into  the  breast  of  a  pigeon.  The  animal 
did  not  exhibit  any  signs  of  active  poisoning,  but  it  died  at  the  end  of  the  fourth 
day. 

"  • 

Alum. — We  made  but  two  experiments  with  alum,  one  with  the  venom  of  the 
Crotalus  liorridus  and  one  with  Cobra. 

Experiment. — Dissolved  0.015  gram  dried  venom  in  0.5  c.  c.  distilled  water  and 
added  3  gtt.  saturated  solution  of  alum  (18°  C.),  but  no  precipitate  occurred;  we 
then  gradually  added  powdered  alum  nearly  to  saturation,  which  caused  precipita- 
tion. The  precipitate  was  filtered  off,  and  the  clear  filtrate  tested  by  the  further 
addition  of  alum  to  see  if  any  more  precipitation  would  occur,  with  a  negative 
result.  The  precipitate  and  filtrate  were  now  mixed  together  and  injected  into  the 
breast  of  a  pigeon  without  any  poisonous  result  occurring  within  forty-eight  hours. 

In  another  experiment  in  which  0.06  gram  of  dried  Crotalus  venom  was  used, 
the  animal  died  in  forty-five  minutes. 


EFFECTS  OF  VARIOUS  AGENTS  ON  VENOM.        37 

Alum  added  to  saturation  does  not  precipitate  the  peptone,  although  it  precipi- 
tates all  of  the  coagulable  proteids. 

The  following  is  the  experiment  with  Cobra  venom: — 

Experiment. — Dissolved  0.015  gram  dried  venom  in  0.5  c.  c.  distilled  water  and 
added  alum  to  saturation  (16°  C.). 

4:32.   Injected  into  the  breast  muscles  of  a  pigeon. 
4:50.  Down. 
4:52.  Dead. 

This  last  experiment  is  of  interest  in  proving  that  even  so  powerful  an  astringent 
as  alum  is  not  sufficiently  strong  to  prevent  the  prompt  absorption  of  the  poison. 
Death  followed  in  twenty  minutes. 

Chlorine  Water. — This  reagent  docs  not  seem  to  exert  any  influence. 

Experiment. — Dissolved  0.015  gram  Crotalus  adamanteus  venom  in  0.5  c.  c.  dis- 
tilled water  and  added  0.5  c.  c.  fresh  chlorine  water. 

4:28.  Injected  into  the  breast  muscles  of  a  pigeon. 
4:52.   Down. 
5:10.   Dead. 

Bromine. — The  action  of  bromine  in  bromohydric  acid  solution  is  very  marked. 

Experiment. — Powdered  0.015  gram  dried  Crotalus  adamanteus  venom  in  a 
mortar  and  added  2  gtt.  of  bromine  in  4  or  5  gtt.  bromohydric  acid,  then  added 
0.5  c.  c.  alcohol. 

5:05.  Injected  into  the  breast  of  a  pigeon. 
5:30.  No  effect. 
Twenty-four  hours.  No  effect. 

This  experiment  was  repeated  once  with  Crotalus  venom  and  once  with  Cobra, 
using  water  as  the  diluent  instead  of  alcohol.  In  both  experiments  we  found  a 
similar  result,  thus  proving  that  the  activity  of  the  venom  is  completely  destroyed 
by  this  reagent. 

Iodine.  Experiment. — Dissolved  0.015  gram  dried  venom  of  Crotalus  ada- 
manteus in  0.33  c.  c.  distilled  water,  then  added  0.5  c.  c.  tr.  iodine  which  formed  a 
dense  brown  precipitate. 

5:07.  Injected  into  the  breast  of  a  pigeon. 
No  poisonous  effects  within  twenty-four  hours. 

If,  however,  the  amount  of  iodine  be  much  smaller  the  venom  is  still  potent,  as 
is  shown  by  the  following  experiment. 

Experiment. — Dissolved  the  venom  as  above,  then  added  1  drop  tr.  iodine  and 
afterwards  1  c.  c.  distilled  water. 

4:56.  Injected  into  the  breast  of  a  pigeon. 
5:05.  Weak. 
5:15.   Dying. 

Iodine  -\-  Potassic  Iodide.  Experiment.— Dissolved  0.015  gram  dried  venom  of 
Crotalus  adamanteus  in  0.5  c.  c.  distilled  water,  then  added  a  saturated  solution  of 
equal  parts  of  tr.  iodine  and  potassic  iodide. 

4:41.. Injected  the  above  into  the  flank  of  a  small  rabbit  (half  grown). 
The  animal  died  in  about  eighteen  hours. 


38"  THE   VENOMS   OF    CERTAIN    T  II  A  N  A  T  O  P  H I D  E  M. 

The  delay  in  the  occurrence  of  death  in  this  experiment  was  considerable,  and 
that  this  was  due  to  the  action  of  the  iodine  on  the  venom  is  rendered  probable 
by  the  results  of  the  preceding  experiments  with  iodine  and  by  the  following 
experiment  with  the  potassic  iodide. 

Potassic  Iodide. — This  salt  does  not  seem  to  exert  any  influence  upon  the  activity 
of  venom. 

Experiment. — Dissolved  0.015  gram  dried  venom  of  the  Crotalus  adamanteus  in 
1  c.  c.  saturated  solution  of  potassic  iodine. 

4:31.   Injected  into  the  breast  of  a  pigeon. 
4:40.  Down. 
4:45.  Dead. 

Potassic  Bichromate.  Experiment. — Dissolved  0.03  gram  dried  Crotalus  ada- 
manteus venom  in  1  c.  c.  distilled  water  and  added  0.01  gram  potassic  bichromate. 

4:14.  Injected  into  the  breast  of  a  pigeon. 

4:20.  Down. 

4:25.   Convulsions  followed  by  death. 

Experiment. — Dissolved  0.004  gram  dried  venom  in  0.5  c.  c.  distilled  water  and 
added  0.03  gram  potassic  bichromate  dissolved  in  0.33  distilled  water,  which  pro- 
duced a  dense  coagulum. 

3:38.   Injected  into  the  breast  muscles  of  a  pigeon. 
4:05.  Dead. 

Potassic  Permanganate.  Experiment. — Dissolved  0.03  gram  dried  Crotalus 
adamanteus  venom  in  0.5  c.  c.  distilled  water  and  added  0.06  gram  permanganate 
in  0.5  c.  c.  distilled  water.  This  formed  a  very  cloudy  solution. 

5:27.   Injected  into  the  breast  of  a  pigeon.     Death  occurred  within  forty-eight  hours. 

Experiment. — The  same,  using  0.015  gram  of  the  permanganate.  At  the  end 
of  the  second  day  no  poisonous  effects  from  the  venom.  The  parts  where  the  injec- 
tion was  made  look  as  though  they  would  slough. 

Experiment. — The  same,  using  0.005  gram  of  the  permanganate.  The  solution 
formed  is  a  dark  wine  color. 

4:37.  Injected  into  the  breast  of  a  pigeon  without  effect. 

Experiment. — The  same,  using  0.0038  gram  of  permanganate. 
4:26.   Injected  as  above. 
4:42.   Down. 
4:45.   Dead. 

Experiment. — The  same,  using  0.0025  gram  of  permanganate. 

3:57.  Injected  as  above. 
4:06.   Down. 
4:10.   Dead. 

In  another  experiment,  the  mixture  was  injected  into  the  femoral  vein  of  a 
rabbit,  using  0.005  gram  permanganate.  The  animal  lived,  and  at  the  end  of  the 
second  day  was  apparently  unaffected. 

In  one  observation  made  with  the  venom  of  the  Crotalus  horridus  0.015  gram 
of  venom  was  dissolved  in  0.5  c.  c.  distilled  water,  to  which  was  afterwards  added 
0.008  gram  of  the  permanganate.  After  standing  for  twenty-four  hours  the 


E  F  F  E  C  T  S    OF    VARIOUS    AGENTS    ON    V  E  N  0  .M .  39 

mixture  was  very  thick  and  tarry,  and  would  not  flow  from  the  inverted  test-tube. 
It  seems  from  this  that  the  full  extent  of  the  action  of  the  permanganate  on  the 
venom  is  not  exerted  for  some  hours. 

The  permanganate  is  efficient  in  destroying  the  activity  of  Cobra  venom. 

Experiment. — Dissolved  0.015  gram  dried  Cobra  venom  in  0.5  c.  c.  distilled  water 
and  added  0.015  gram  permanganate. 

4:35.   Injected  into  the  breast  muscles  of  a  pigeon.     No  symptoms  of  venom  poisoning 
within  twenty-four  hours. 

Peroxide  of  Hydrogen. — Notwithstanding  the  powerful  nature  of  the  peroxide 
of  hydrogen  as  an  oxidizer,  it  does  not  seem  to  affect  to  any  great  extent  the 
poisonous  activity  of  venom.  Only  one  experiment  was  made. 

Experiment. — Added  3  drops  of  fresh  venom  of  the  Crotalus  adamanteus  to  3 
c.  c.  fresh  solution  of  peroxide  of  hydrogen,  specially  prepared  by  Prof.  Leeds,  of 
Hoboken. 

5:05.   Injected  into  the  breast  muscles  of  a  pigeon. 

5:15.   Unable  to  stand;  decided  local  effects  appearing. 

6:05.   Dead,  with  all  the  usual  phenomena  of  venom  poisoning. 

The  quantity  of  peroxide  of  hydrogen  used  in  this  experiment  was  so  large  that 
the  test  was  a  satisfactory  one. 

Argentic  Nitrate. —  Notwithstanding  the  powerful  action  of  nitrate  of  silver  on 
albuminoids  it  does  not  seem  to  possess  great  power  to  disturb  the  toxicity  of 
venom. 

Experiment. — Dissolved  0.015  gram  of  dried  venom  of  Crotalus  adamantem  in 
3  c.  c.  distilled  water,  to  which  was  afterwards  added  0.015  gram  nitrate  of  silver, 
forming  a  decidedly  milky  solution. 

4:40.  Injected  into  the  breast  of  a  pigeon. 
4:50.   Down  ;  deep  breathing,  gasping. 
4:53.   Dead. 

As  there  was  a  possibility  of  the  quantity  of  salt  being  insufficient  for  the  amount 
of  venom,  another  experiment  was  made  in  which  double  the  weight  of  nitrate 
was  used.  The  mixture  was  injected  into  the  breast  of  a  pigeon.  At  the  end  of 
three  days  no  symptoms  of  venom  poisoning  had  occurred. 

Mercuric  Chloride. — When  mercuric  chloride  is  added  to  a  solution  of  Crotalus 
or  Moccasin  venom  a  dense  precipitate  occurs,  consisting  of  all  the  proteids  in 
solution.  In  order  to  learn  if  the  precipitated  proteids  still  retained  any  toxic 
power  we  dissolved  0.03  gram  of  dried  venom  of  the  Crotalus  adamanteu*  in  1 
c.  c.  distilled  water  and  then  added  0.03  gram  mercuric  chloride.  The  precipitate 
was  collected  on  a  filter  and  repeatedly  washed  with  distilled  water.  During  this 
washing  the  precipitate  seemed  to  diminish  a  little  in  quantity,  and  was  no  doubt 
partially  dissolved. 

3:30.  The  precipitate  in  1  c.  c.  distilled  water  was  injected  into  the  breast  of  a  pigeon. 

6:00.  No  symptoms  up  to  this  time. 

Twenty-four  hours — the  animal  showed  no  signs  of  venom  poisoning. 

Ferrous  Sulphate. — Three  experiments  were  made  with  the  sulphate  of  iron 
with  results  materially  different ;  the  difference  no  doubt  depending  upon  the  mode 


40  THE   VENOMS    OF   CERTAIN   THANATOPHIDE^E. 

of  administration.  In  all  the  same  quantities  of  venom  and  salt  were  used,  but  in 
one  the  solution  was  injected  simply  beneath  the  skin  and  in  the  others  directly 
into  the  muscles  of  the  breast.  In  the  former  the  animal  did  not  die  until  after 
the  lapse  of  nearly  thirty-six  hours,  while  one  of  the  others  died  remarkably  soon 
— within  four  minutes  after  the  injection,  and  the  third  in  twenty-eight  minutes. 

Experiment. — Dissolved  0.03  gram  dried  venom  of  the  Crotalus  adamanteus  in 
1  c.  c.  distilled  water  and  then  added  0.03  gram  ferrous  sulphate.  The  addition 
of  the  iron  salt  renders  the  solution  clear. 

3:40.  Injected  beneath  the  skin  of  the  thigh  of  a  pigeon. 
6:00.  No  apparent  effects. 

Twenty -four  hours — no  effects.      Thirty-six  hours — dead.     Slight  local  effects  of  venom, 
but  the  destructive  action  of  the  iron  salt  on  the  tissues  is  much  more  prominent. 

Experiment. — The  same  as  above. 

3:32.   Injected  into  (he  breast  muscles  of  a  pigeon. 
3:36.   Convulsions  :  death.     No  local  lesions. 

•  . 

In  another  experiment  the  bird  died  in  twenty-eight  minutes  after  injection. 

It  must  be  concluded  from  this  that  the  ferrous  sulphate  does  not  destroy  the 
activity  of  the  venom. 

Dialyzed  Iron. — When  dialyzed  iron  is  added  to  a  solution  of  venom  all  of  the 
proteid  matter  is  precipitated,  and  the  filtrate  is  found  to  give  no  reaction  for 
proteids  with  the  xanthoproteic  or  picric-acid  tests.  The  precipitate  is  brown,  and 
so  gelatinous  that  if  the  solutions  are  somewhat  concentrated  it  does  not  flow. 
The  precipitate  does  not  dissolve  in  distilled  water,  yet  it  must  be  very  soluble  in 
the  tissues  since  the  toxic  effects  of  the  venom  rapidly  appear  after  its  injection. 
We  made  two  experiments,,  both  with  Moccasin  venom,  one  with  the  dried  and  the 
other  with  fresh  venom. 

Experiment. — Dissolved  0.015  gram  dried  Moccasin  venom  in  0.5  c.  c.  distilled 
water  and  added  3  gtt.  dialyzed  iron.  This  caused  a  considerable  amount  of 
brownish  gelatinous  precipitate  which  thickened  the  mixture  appreciably.  Now 
added  1  c.  c.  distilled  water. 

'3:20.  Injected  into  the  breast  muscles  of  a  pigeon. 
3:25.   Down. 
3:45.  Dead. 

Experiment. — Took  two  drops  of  fresh  Moccasin  venom  and  added  first  5  gtt. 
dialyzed  iron,  and  then  1  c.  c.  distilled  water.  The  iron  and  venom  made  a  very 
thick  brownish  mixture. 

5:18.  Injected  into  the  breast  muscles  of  a  pigeon. 
5:30.  Dead. 

One  experiment  was  made  in  this  connection  to  see  if  dialyzed  iron  exerted 
any  poisonous  effect,  we  injected  thirty  drops  into  the  breast  muscles  of  a  pigeon, 
without  toxic  result. 

Ferric  Chloride. — We  have  used  the  chloride  of  iron  in  two  forms;  the  officinal 
tincture,  U.  S.  P.,  and  the  officinal  liquor.  Both  these  solutions  greatly  affect  the 
poisonous  activity  of  venom,  the  latter,  indeed,  if  used  in  sufficient  quantity, 


EFFECTS   OF  VARIOUS  AGENTS   ON   VENOM.  41 

wholly  prevents  the  occurrence  of  any  of  the  symptoms  of  venom  poisoning.     The 
tincture  does  not  appear  to  be  nearly  as  efficient. 

Experiment. — Dissolved  0.015  gram  dried  venom  of  the  Crotalus  adamanteus  in 
0.5  c.  c.  distilled  water  and  added  10  gtt.  tr.  chloride  of  iron.  As  the  iron  was 
added  the  solution  cleared,,  but  in  a  few  moments  became  milky,  and  finally  thick 
with  whitish  precipitate. 

4:22.  Injected  into  the  breast  of  a  pigeon. 

5:00.  No  symptoms. 

5:45.  No  symptoms. 

Following  morning — dead.     No  local  effect. 

In  two  similar  experiments,  in  which  double  the  quantity  of  the  tincture  of  iron 
was  used,  the  result  was  much  the  same,  the  time  of  death  being  notably  delayed. 
The  following  experiments  were  made  with  the  liquor: — 

Experiment, — Dissolved  0.015  gram  dried  venom  of  Crotalus  adamanteus  in  0.5 
c.  c.  distilled  water  and  added  4  gtt.  liquor  ferri  chloridi.  A  heavy  precipitate 
fell. 

4:45.  Injected  into  the  breast  of  a  pigeon. 

5:00.  Very  quiet. 

G:00.  No  symptoms,  and  none  of  venom  poisoning  within  two  days. 

A  similar  experiment  was  made  with  identical  results. 

In  one  experiment  with  the  venom  of  the  Crotalus  horridus,  in  which  only  two 
drops  of  the  liquor  were  used,  the  animal  showed  no  evidences  of  poisoning;  and 
in  four  experiments  made  with  the  dried  venom  of  the  Moccasin,  in  which  0.015 
gram  of  dried  venom  was  used  and  eight,  four,  two,  and  one  drop  of  the  liquor 
were  used,  three  animals  gave  no  symptoms  of  venom  poisoning,  and  one  died  on 
the  third  day — the  animal  receiving  the  injection  containing  but  one  drop  of  the 
iron.  This  was  the  only  pigeon  of  the  four  which  gave  any  signs  of  poisoning. 
In  three-fourths  of  an  hour  the  bird  was  shaky,  and  at  the  end  of  three  hours 
decidedly  feeble,  remaining  pretty  much  in  this  condition  until  death." 

About  the  point  of  injection  the  iron  produced  considerable  hardening  of  the 
tissues. 

The  effect  on  Cobra  venom  is  not  marked,  although  in  one  experiment  there 
was  an  appreciable  delay  in  the  occurrence  of  death;  but  in  the  other,  in  which 
the  quantity  of  iron  was  larger,  death  occurred  with  remarkable  rapidity. 

Experiment. — Dissolved  0.015  gram  dried  Cobra  venom  in  0.5  c.  c.  distilled 
water  and  added  2  drops  liquor  ferri  chlor.  A  slight  precipitate  occurred  in  the 
solution  after  a  few  moments. 

3:41.  Injected  into  the  breast  muscles  of  a  pigeon. 
4:15.   Convulsions. 
4:27.  Dead. 

Experiment. — Dissolved  0.015  gram  dried  Cobra  venom  in  1  c.  c.  distilled  water 
and  added  5  gtt.  sol.  perchloride  of  iron. 

This  was  injected  into  the  breast  of  a  pigeon,  with  the  result  of  death  in  twenty 
seconds. 

The  reason  why  ferric  chloride  is  inefficient  in  destroying  the  toxicity  of  Cobra 
venom  no  doubt  lies  in  the  fact  of  its  main  poisonous  substance  being  a  peptone, 

6       April,  1886. 


42  THE   VENOMS   OF   CERTAIN    THANATOPHIDEvE. 

and,  like  that  element  in  all  the  venoms,  unaffected  by  the  iron,  while  the  principal 
toxic  effects  of  the  Crotalus  and  Ancistrodon  venoms  is  due  to  the  globulins  which 
are  precipitated  and  chemically  altered  by  the  iron  salt. 

Filtration  through  Various  Substances. — Filtration  through  alumina  or  wood 
charcoal  does  not  affect  the  poisonous  activity  of  the  venom,  but  by  filtration 
through  animal  charcoal  all  of  the  poisonous  material  in  venom  is  left  behind  and 
the  filtrate  is  accordingly  innocuous. 

Experiment. — Dissolved  0.03  gram  dried  Moccasin  venom  in  2  c.  c.  distilled 
water  and  filtered  four  times  through  animal  charcoal.  The  filtrate  gives  no 
proteid  reaction. 

4:20.  Injected  1.5  c.  c.  of  the  filtrate  into  the  breast  of  a  pigeon.  At  the  end  of  twenty- 
four  hours  no  symptoms  of  venom  poisoning  had  occurred,  but  there  was  some  oedema  at  the 
point  of  injection. 

Repeated  the  above  experiment,  using  0.045  gram  of  Moccasin  venom,  and  with 
similar  results. 

Snake  Bile. — Among  the  curious  substances  which  have  been  extolled  as  anti- 
dotes for  venom  poisoning  is  snake  bile.  We  made  but  one  experiment,  which 
speaks  volumes. 

Experiment. — Mixed  1|  minims  of  fresh  venom  from  a  dead  Crotahis  adam- 
anteus  with  1  c.  c.  of  bile  from  the  same  animal. 

4:47.     Injected  into  the  breast  of  a  pigeon. 
4:47^.   Incoordination. 
4:50.     Gasping  respiration. 
4:55.     Convulsive  movements. 
4:56.     Dead. 

Digestion. — By  digestion  in  strong  artificial  (jastiic  juice  made  from  the  pig's 
stomach  the  toxic  power  of  venom  (Crotalus)  is  completely  destroyed. 

Experiment. — Three  drops  of  the  glycerine  solution  of  venom  (  Crotalus  liorridus) 
(1862)  were  digested  for  sixteen  hours  in  about  1  c.  c.  fresh  artificial  gastric  juice 
from  the  pig's  stomach.- 

8:30  A.  M.  Injected  into  the  breast  muscles  of  a  pigeon.  Up  to  the  end  of  forty-eight 
hours  no  poisonous  symptoms  ensued. 

This  experiment  was  repeated  with  an  identical  result.  We  also  made  two 
experiments  in.  which  the  digestive  process  was  not  carried  on  for  such  a  length 
of  time,  in  both  only  four  hours,  and  with  similar  results.  In  one  we  used  six 
drops  of  the  glycerine  solution  of  venom  as  above — just  double  the  dose — and  in 
the  other  0.015  gram  of  the  dried  Crotalus  adamanteus  venom. 

The  results  of  digestion  in  artificial  pancreatic  juice  are  similar.  We  made  but 
one  experiment,  and  that  with  the  venom  of  the  Crotalus  adamanteus. 

Experiment. — Digested  0.03  gram  dried  venom  in  1  c.  c.  freshly  prepared  pan- 
creatic juice  from  the  pig  for  twenty-four  hours. 

3:44.   Injected  into  the  breast  muscles  of  a  pigeon. 

5:45.   Slightly  droopy. 

Following  morning,  no  effects  apparent. 


EFFECTS  OF  VARIOUS  AGENTS  ON  VENOM.        43 

Resume. — The  above  experiments,  with  others  too  numerous  for  detail,  have 
enabled  us  to  confirm  Lacerda's  and  Vincent  Richard's  views  as  to  the  power  of 
permanganate  of  potassium  to  destroy  venoms.  As  a  local  antidote  it  is  for  all 
snake  poisons  the  best. 

It  is  also  clear  from  what  we  have  seen  that  ferric  chloride  is  a  very  efficient 
local  destroyer  of  the  venom  of  our  own  snakes,  which  owe  their  vigor  to  venom- 
globulin,  but  has  little  value  as  a  local  antidote  to  the  peptone  which  gives  power 
to  the  poison  of  the  Cobra.  The  chloride  needs  to  be  locally  used  in  full  doses, 
whence  it  is  that  the  strong  liquor  ferri  chloridi  (U.  S.  P.)  is  more  efficient  than 
the  tincture. 

That  bromine  may  prove  valuable  as  a  local  means  of  relief  seems  to  be  plain 
from  our  experiments,  and  is  in  fact  one  of  their  most  interesting  results.  It  was 
used,  as  we  have  seen,  either  as  hydrobromic  or  bromohydric  acid.  Probably  any 
solution  of  bromine  would  answer,  and — as  was  shown  by  its  free  local  use  to  control 
gangrene  during  our  civil  war — there  need  be  no  fear  in  using  it  with  freedom. 

It  has  long  been  known  in  India  that  the  strong  alkalies  destroy  venom,  and 
this  we  are  able  to  confirm.  Brainerd  long  ago  taught  that  iodine  has  destructive 
value  as  regards  Crotalus  venom,  and  this  also  seems  to  us  to  be  true. 

In  fact  many  agents  more  or  less  alter  venoms  if  allowed  to  remain  long  in  con- 
tact with  them,  and  usually  act  with  increased  vigor  as  the  temperature  is  raised 
above  that  of  the  air ;  but  it  is  chemically  singular  that  brief  exposure  of  venoms 
to  strong  acids  should  so  little  affect  the  toxicity  of  the  poisons  in  question. 
Except  where  otherwise  distinctly  stated,  the  chemicals  used  by  us  have  been 
added  to  the  poison  immediately  before  injecting  it.  Enough  has  been  here 
proved  to  make  it  now  worth  while  to  study  jstill  more  carefully  the  value  of 
bromine  and  ferric  chloride  as  local  poison  destroyers.  One  agent  may  be  at  hand 
or  available  when  others  are  not,  and  the  more  numerous  are  the  means  we  possess 
as  local  antidotes  the  better  is  the  chance  of  escape  or  relief  for  persons  bitten. 


44  THE    VENOMS   OF   CERTAIN   TH  AN  A  T  0  PHID 


CHAPTER    IV. 

THE  EFFECTS  OF  VENOM  WHEN  APPLIED  TO  MUCOUS  OR 
SEROUS  SURFACES. 

The  Effects  of  Venom  when  applied  to  Mucous  .Surfaces. — The  question  of  the 
absorption  of  venom  by  mucous  surfaces  is  one  of  great  interest,  and  the  verdict 
of  all  observers  in  connection  with  the  venom  of  the  Crotalidae  is  that  uninjured 
mucous  surfaces,  except  in  the  lungs,  cannot  absorb  venom,  at  least  in  sufficient 
quantities  to  produce  death.  In  experiments  with  the  venom  of  the  Cobra  other 
investigators  have  gotten  results  which  are  directly  contrary,  but  in  our  own 
researches  a  large  proportion  of  the  animals  survived. 

In  seven  experiments  made  on  pigeons,  in  which  a  solution  of  Cobra  venom  was 
placed  in  the  craw  by  means  of  an  cesophageal  tube,  six  showed  no  evidences  of 
poisoning  and  one  died.  In  these  experiments  the  cesophageal  tube,  which  was  a 
small  catheter,  was  oiled  and  passed  with  great  care  into  the  crop,  the  solution  of 
venom  was  then  poured  through  the  tube  by  means  of  a  funnel,  and  afterwards 
washed  down  with  a  little  water. 

Experiment. — Dissolved  0.025  .gram  dried  Cobra  (Naja  trip.')  in  about  1  c.  c. 
distilled  water,  and  placed  it  in  the  crop  of  a  pigeon  by  means  of  an  cesophagcal 
tube.  Up  to  four  days  the  animal  showed  no  signs  of  poisoning. 

Five  other  experiments,  like  the  above,  gave  identical  results.  In  one  experi- 
ment the  animal  died  within  twelve  hours. 

Experiment. — Dissolved  0.013  gram  dried  Cobra  (Naja  trip.)  in  about  1  c.  c. 
distilled  water  and  gave  to  a  pigeon,  as  above,  at  4:00  p.  M.  A  little  while  after 
the  dose  the  pigeon  appeared  sickish  and  remained  in  much  the  same  condition 
for  about  two  hours,  when  observation  temporarily  ceased.  At  8:30  the  following 
morning  the  bird  was  dead.  The  heart  was  found  in  systole  and  contained  dark 
clots.  The  blood  was  everywhere  coagulated.  No  apparent  lesions  were  present 
in  any  part  of  the  body,  and  a  most  careful  examination  of  the  mouth,  gullet,  and 
crop  revealed  no  abrasions  or  other  raw  surface.  The  crop  contained  a  little  cracked 
corn  and  a  small  amount  of  yellowish  fluid. 

In  another  pigeon,  etherized,  an  opening  was  made  through  the  skin  into  the 
craw,  and  its  contents  washed  out.  The  pigeon  was  kept  on  its  back  and  the 
edges  of  the  wound  were  held  up  by  retractors.  A  solution  of  venom  was  placed 
in  the  cul-de-sac  on  the  left  side  and  the  animal  watched.  In  a  half  hour  the 
bird  had  convulsive  seizures,  and  at  the  end  of  forty  minutes  was  dead.  At  that 
time  there  seemed  to  be  about  the  same  quantity  of  venom  solution  in  the  crop  as 
before.  It  was,  however,  somewhat  glutinous  and  darker  in  color.  The  mucous 


THE   EFFECTS   OF   VENOM.  45 

• 

membrane  preserved  its  natural  tint.  On  the  side  in  which  was  the  poison  the 
mucous  membrane  was  wrinkled  and  raised  in  points  like  the  surface  of  a  mul- 
berry. By  stretching  the  mucous  membrane  this  roughness  disappeared.  After 
death  it  increased  somewhat.  There  was  no  oedema. 

Experiment. — 0.01  gram  of  dried  Cobra  dissolved  in  a  little  water  was  given  to 
a  frog  by  an  cesophageal  tube  as  in  the  case-  of  the  pigeons.  The  frog  presented 
no  toxic  symptoms  for  two  hours.  After  twelve  hours  it  was  dead.  . 

Autopxjj. — All  the  tissues  had  a  cyanotic  appearance  and  the  animal  was  perfectly 
flaccid.  '  The  heart  was  still  irritable  as  well  as  the  intestines.  The  stomach  con- 
tained a  viscid  mass  of  mucus,  which  was  not  bloody,  and  which  was  expelled  from 
the  stomach  by  the  normal  contractility  when  the  organ  was  cut.  A  most  careful 
examination  of  the  mouth,  gullet,  and  mucous  membrane  of  the  stomach  did  not 
reveal  any  abrasions  or  other  raw  surface.  The  liver  seemed  pale  and  decidedly 
friable. 

In  Dr.  Mitchell's  former  experiments  made  in  the  opened  crop,  fatal  results  did 
not  occur  with  use  of  fresh  or  dry  venom  of  Crotali ;  but  a  single  needle  pricked 
through  the  mucous  surface  covered  by  the  poison,  sufficed  to  let  in  death. 

It  seems  possible  that  minute  ulcers  or  abrasions,  quite  invisible  to  the  eye, 
might,  in  like  manner,  enable  the  venom  in  some  cases  to  pass  the  barrier  of  the 
intestinal  mucous  lining.  The  deaths  from  ingested  Cobra  venom  related  by 
Fayrer  took  place  in  mammals,  and  we  ourselves  found  in  like  experiments  with 
rabbits,  that,  although  death  was  rare  after  swallowing  Cobra  venom,  it  was  less  so 
than  in  pigeons;  but  our  Cobra  experiments  are  not  strictly  comparable  with  those 
done  in  India  with  fresh  poison. 

Certainly  Cobra  venom  is  much  more  apt  to  kill  when  swallowed  than  is  Cro- 
talus  poison.  In  the  rattlesnake  it  is  the  globulins  which  are  in  largest  amount, 
and  which  are  not  dialysable,  but  in  Cobra  the  fatal  peptone  is  the  material  which, 
both  as  to  vigor  and  amount,  represents  the  poisoning  capacity,  and  is  as  we  know 
dialysable.  It  is  only  astonishing,  therefore,  that  it  does  not  kill  in  every  case  in 
which  it  is  swallowed;  but,  as  we  have  seen,  the  gastric  juices  in  so  far  as  they 
have  time  to  act  are  destructive  of  venoms,  and  hence  their  protective  agency  has 
also  to  be  considered. 

The  Activity  of  Venom  when  applied  to  Serous  Surfaces. — One  of  the  most 
remarkable  and  interesting  of  the  physiological  effects  produced  by  the  venom  of 
the  Crotalus  is  the  occurrence  of  ecchymoses,  especially  in  the  serous  tissues.  The 
character  of  these  ecchymoses  is  fully  treated  in  another  part  of  the  work,  so  that 
we  need  here  only  detail  some  of  our  observations  in  connection  with  the  direct 
effect  of  the  application  of  venom  to  the  serous  tissues. 

A  rabbit  was  etherized  and  kept  in  this  condition  during  the  whole  of  the 
experiment.  The  abdominal  cavity  was  opened  and  a  knuckle  of  intestine 
exposed.  On  the  peritoneum  were  placed  a  few  small  particles  of  the  dried 
venom  of  the  Crotahw  adamanteus.  In  two  or  three  minutes  some  extravasations 
appeared  immediately  about  the  point  of  the  application  of  the  venom;  a  few 
moments  later  these  extravasations  were  diffused  over  a  considerable  area  and  had 
run  into  each  other  to  such  an  extent  as  to  form  a  patch  of  bleeding  surface.  So 


46  THE    VENOMS   OF    CERTAIN   THANATOPHIDE^E. 

rapidly  do  these  hemorrhages  spread  that  they  can  literally  be  seen  to  grow  under 
the  eye.  Another  portion  of  the  intestine  was  exposed,  and  upon  the.  peritoneum 
was  placed  a  very  small  portion  of  the  glycerine  solution  of  venom  (prepared  in 
1862),  which  has  already  been  referred  to.  Ten  minutes  after  the  application 
small  points  of  extravasation  appeared,  and  in  three  minutes  more  had  increased 
so  much  in  number  and  spread  so  rapidly  as  to  form  a  continuous  area  of  bleeding 
surface.  Four  drops  of  the  glycerine  solution  of  venom  in  a  little  water  were 
boiled  and  carefully  evaporated  to  a  thick  paste  and  then  applied  to  a  fresh  surface 
of  the  peritoneum.  After  one  hour  no  ecchymoses  appeared. 

In  another  experiment  0.03  gram  of  the  dried  Moccasin  venom  was  boiled  and 
injected  into  the  peritoneal  cavity  of  a  pigeon.  The  animal  died  in  forty-two 
minutes,  when  we  found  large  ecchymoses  scattered  over  all  the  abdominal  viscera. 
In  later  experiments  we  have  fully  determined  that  the  venom  peptone  may  cause 
ecchymoses,  but  that  this  power  exists  in  an  insignificant  degree  as  compared  with 
that  of  the  globulins. 

In  another  experiment,  not  irrelevant  here,  we  injected  one  drop  of  the  fresh 
venom  from  the  Crotalus  adamanteus  into  one  of  the  mesenteric  arteries  of  an 
etherized  rabbit.  In  a  few  seconds  ecchymotic  patches  appeared  on  the  large 
intestine  followed  by  a  few  on  the  small  intestine,  and  in  another  moment  the 
animal  was  dead. 

In  an  experiment  on  an  alligator,  elsewhere  quoted,  the  activity  with  which 
venom  may  be  absorbed  by  serous  membranes  is  well  illustrated.  In  a  frog 
death  occurred  within  two  hours  after  the  injection  of  two  drops  of  the  fresh 
venom  of  the  Crotalus  adamanteus  into  the  peritoneal  cavity. 

In  one  experiment  made  upon  an  etherized  rabbit  in  which  1  drop  of  fresh  Moc- 
casin venom  was  dissolved  in  1.5  c.  c.  of  distilled  water  and  injected  into  the 
peritoneal  cavity  the  animal  died  in  one  and  a  quarter  hours.  In  an  autopsy  one 
hour  after  death,  it  was  found  that  there  was  no  rigor  mortis ;  the  whole  of  the 
inside  of  the  peritoneal  cavity  was  stained,  and  in  places  was  literally  dripping 
with  blood ;  the  mesentery  contained  a  large  amount  of  blood  resembling  a  free 
clot.  On  the  surface  of  the  intestines  the  effusion  of  blood  was  of  a  brilliant  red 
color  as  though  from  the  arterioles ;  the  whole  interior  of  the  abdominal  cavity 
was  stained ;  the  heart  was  arrested  in  systole. 

In  still  another  experiment  in  which  the  solution  of  venom  was  boiled  the  results 
were  strikingly  different.  We  dissolved  0.03  gram  of  dried  Moccasin  venom  (repre- 
senting a  much  greater  dose  than  was  given  in  the  previous  experiment)  and  after 
boiling  it  for  a  moment  filtered  it.  The  filtrate  was  injected  into  the  peritoneal 
cavity  of  a  rabbit.  The  animal  was  killed  after  the  lapse  of  one  hour  and  the 
peritoneal  cavity  examined.  There  were  absolutely  no  alterations  to  be  seen  in 
the  viscera,  excepting  one  minute  spot  where  there  appeared  a  little  reddening. 

The  length  of  time  during  which  the  venom  used  was  boiled  was  not  distinctly 
stated  in  the  notes  of  some  of  our  observations.  The  omission  was  of  moment. 

At  the  time  these  experiments  were  made,  we  did  not  fully  know  that  while  in 
all  venoms — brief  boiling  throws  down  the  globulins  at  once — much  longer  boiling 
by  degrees  precipitates,  and  at  last  makes  innocent  the  peptones.  Apparently  it 


THE    EFFECTS    OF    VENOM.  47 

is  the  globulins  which  most  rapidly  alter  blood  and  vessels,  and  by  a  mechanism 
hereinafter  to  be  described  cause  ecchymoses.  Yet  are  the  peptones  not  without 
this  toxic  capacity,  as  is  seen  in  some  of  the  above  observations.  Clearly,  however, 
boiling  impairs  the  activity  of  Crotaline  peptones,  as  it  does  that  of  like  constitu- 
ents of  Cobra  poison.  It  will  have  been  seen  that  none  of  these  direct  experiments 
on  serous  tissues  were  made  with  pure  or  boiled  Cobra  venom.  It  is  desirable  that 
this  should  be  done,  and  especially  with  fresh  venom.  In  another  portion  of  this 
paper  there  are  some  relative  studies  of  the  power  of  dried  Cobra  and  Rattlesnake 
venoms  to  cause  local  hemorrhages  from  the  peritoneum.  In  the  former  work  of 
Dr.  Mitchell,  and  in  that  of  Fayrer  and  Brunton,  are  sufficient  studies  of  the  ab- 
sorbing power  of  rectal  and  pulmonary  surfaces  and  of  the  eye. 


48  THE   VENOMS   OF   CERTAIN    T  H  AN  AT  0  P  HI  D  E  M. 


CHAPTER    V. 

THE  EFFECTS  OF  VENOM  ON  THE  NERVOUS  SYSTEM. 

EXCEPTING  as  regards  the  marked  action  OH  the  respiratory  centres  we  cannot 
consider  venom  as  essentially  or  solely  a  nerve  poison.  In  animals  which  do  not 
immediately  die  from  the  effects  of  this  poison,  the  first  signs  of  nerve  poisoning 
are  drowsiness,  incoordination,  followed  by  loss  of  voluntary  motion,  by  convul- 
sions, or  failure  of  reflex  activity  and  by  death. 

Reflex  Action. — In  six  experiments  on  frogs  with  the  Crotalus,  made  in  connec- 
tion with  a  direct  study  of  the  effect  on  reflex  action,  in  none  of  them  was  there 
found  a  slow,  gradual  diminution  of  reflex  activity,  but  invariably  a  sudden  loss  of  this 
function.  The  time  of  the  occurrence  of  the  loss  of  reflex  activity  varies  very 
greatly.  In  four  experiments  on  pithed  frogs,  each  of  the  frogs  was  given  0.015 
gram  of  the  dried  Crotalus  adamanteus  venom  in  10  minims  of  distilled  water, 
by  means  of  injection  into  the  posterior  lymph  sac.  In  one  experiment  no 
alteration  in  reflex  activity  occurred  after  one  and  three-quarter  hours,  although  it 
seems  probable  that  the  venom  was  not  by  any  means  completely  absorbed  since 
the  lymph  sac  seemed  bulged  with  fluid  which  had  accumulated.  In  another 
experiment  no  alteration  occurred  in  one  and  a  half  hours.  In  a  third  reflex  action 
was  suddenly  abolished  in  one  hour,  and  in  a  fourth  in  forty-five  minutes,  without 
there  being  in  any  case  gradual  diminution  of  reflex  activity  preceding  the  com 
plete  loss. 

Two  experiments  were  made  on  pithed  frogs  to  determine  if  the  loss  of  reflex 
activity  was  due  to  an  action  of  the  venom  upon  the  nerves  or  upon  the  spinal 
cord,  and  for  this  purpose  we  ligated  all  of  the  bloodvessels  in  the  right  hind  leg 
of  each  animal,  and  thus  prevented  the  access  of  the  venom  to  these  parts.  To 
each  of  these  frogs  was  given  0.015  gram  of  the  dried  venom  of  the  Crotalus 
adamanteus  dissolved  in  5  minims  of  distilled  water,  and  injected  into  the  posterior 
lymph  sac.  Reflex  activity  suddenly  ceased  in  both  of  the  frogs  in  one  and  a  half 
hours.  No  reflex  action  was  elicited  by  irritation  of  the  nerves  of  either  leg, 
although  the  motor  fibres  of  the  nerves  were  very  excitable.  We  also  found  that 
direct  excitation  of  the  spinal  cord  in  the  dorsal  region  produced  movements  in 
the  posterior  extremities,  but  none  in  the  anterior  extremities,  thus  showing  that 
impulses  could  travel  down  the  cord  through  the  motor  apparatus  but  not  upwards 
through  the  sensory  portions.  These  observations  make  it  clear  that  the  loss  of 
reflex  activity  is,  no  doubt,  dependent  to  a  great  extent  at  least  upon  an  action  of 
the  venom  upon  the  sensory  portions  of  the  cord,  although  it  is  not  clear  that  the 
sensory  nerve  fibres  may  not  also  be  seriously  affected. 


EFFECTS    OF   VENOM    ON    THE   NERVOUS    SYSTEM.  49 

Senior y  and  Motor  Nerves. — In  order  to  more  directly  test  the  action  of  venom 
upon  the  motor  and  sensory  fibres  we  exposed  the  sciatic  nerve  along  the  whole 
extent  of  the  thigh  of  pithed  frogs,  and  placed  in  the  middle  of  the  exposed  trunk 
a  little  (Crotalus)  venom  (concentrated  by  spontaneous  evaporation).  Comparative 
observations  were  now  made  from  time  to  time  by  exciting  the  mixed  nerve  trunk 
above  and  below  the  point  of  application  of  the  venom  by  means  of  electrodes 
connected  with  a  Du  Bois-lteymond  induction  coil,  using  minimum  strengths  of 
current.  After  about  fifteen  minutes,  irritation  of  the  foot  of  the  leg  with  the 
poisoned  nerve  did  not  give  as  good  reflexes  as  irritation  of  the  other  leg.  After 
five  hours,  irritation  of  the  trunk  of  the  nerve  below  the  poisoned  part  did  not 
give  reflexes,  but  above  the  part  did  give  reflexes,  showing  that  the  sensory  fibres 
were  functionally  destroyed  by  the  local  application  of  the  poison.  When  the 
trunk  was  irritated  above  the  poisoned  part  marked  contraction  of  the  muscles  of 
the  limb  occurred,  showing  that  the  motor  fibres  and  muscles  were  still  intact. 
After  the  lapse  of  six  hours  the  motor  nerves  would  no  longer  respond  to  stimulus, 
although  the  muscles  were  still  irritable. 

From  these  observations  it  seems  obvious  that  both  the  sensory  and  motor  nerves 
are  affected  by  the  poison,  and  that  the  sensory  nerves  are  far  more  susceptible 
than  the  motor  nerves,  and  that  the  depression  of  the  sensory  nerves  may  be  con- 
nected with  the  depression  of  reflex  activity;  but  it  seems  more  than  likely  that 
the  loss  of  reflex  activity  is  essentially  of  spinal  origin,  since  there  is  not  a  slow, 
gradual  diminution  of  reflex  activity  but  a  sudden  paralysis — a  characteristic  which 
may  be  considered  almost  exclusively  spinal. 

Tlie  Spinal  Cord. — We  have  already  stated  that  the  motor  columns  of  the  cord 
remain  irritable  after  complete  paralysis  of  the  sensory  columns.  We  have 
supplemented  these  observations  by  some  experiments  showing  the  direct  action 
of  venom  upon  the  exposed  spinal  cord,  which  prove  that  the  motor  columns  them- 
selves ultimately  succumb  to  the  poison.  In  two  experiments  made  upon  large 
frogs,  in  which  was  laid  bare  the  spinal  cord  in  the  dorsal  region  and  in  which 
the  animals  were  left  to  fully  recover  from  the  shock,  a  concentrated  solution  of 
the  dried  venom  of  the  Crotalus  adamanteus  was  placed  on  a  small  portion  of  the 
cord.  Before  the  application  of  the  venom  the  cord  responded  actively  to  slight 
mechanical  irritation;  after  the  application  of  the  venom  there  occurred  a  gradual 
impairment  in  irritability  for  the  first  fifteen  minutes ;  this  impairment  increased, 
so  that  at  the  end  of  two  hours  the  cord  would  not  respond  to  moderate  electrical 
stimulus.  The  diminution  of  function  continued  until  at  the  end  of  seven  hours 
the  strongest  current  induced  no  response,  although  the  motor  nerve  trunks 
responded  actively. 

Voluntary  Motion. — Usually  the  earliest  signs  of  nerve  poisoning  with  venom 
are  a  disturbance  of  coordination  and  loss  of  voluntary  motion.  In  frogs  we  found 
that  as  long  as  voluntary  motion  lasted  the  reflexes  were  active,  but  that  with  a  loss 
of  volition  reflexes  were  at  once  decidedly  diminished  and  suddenly  disappeared.  In 
frogs  in  which  the  abdominal  aorta  was  ligated  so  as  to  prevent  the  poison  from 
affecting  the  nerves  of  the  posterior  extremities,  the  results  were  similar. 

In  a  number  of  observations  made  upon  mammals  the  above  conclusions  were 

7       April,  1880. 


50  THE    VENOMS    OF    CERTAIN    T  H  A  N  A  T  0  P  II I  D  E  M. 

borne  out.  We  have  also  found  that  the  orbital  reflexes  are  completely  gone  before 
death,  and  that  before  their  loss  voluntary  motion  disappears.  Moreover,  if  the 
spinal  cord  is  irritated  immediately  after  the  cessation  of  the  orbital  reflexes  it  will 
be  found  that  irritation  will  give  rise  to  movements  in  the  posterior  extremities 
only,  and  that  after  the  cord  will  no  longer  respond  to  irritation  the  motor  nerves 
are  still  excitable.  After  the  motor  nerves  cease  to  respond  the  muscles  remain 
irritable. 

These  results  all  go  to  establish  the  conclusion  that  the  respiratory  centre  is  the 
most  vulnerable  point  of  the  nervous  system,  that  the  coordinating  and  volitional 
centres  are  then  prominently  affected,  that  the  sensory  part  of  the  spinal  cord  and 
the  sensory  nerves  are  next  attacked,  and  that  the  motor  parts  of  the  cord,  and 
the  motor  nerves  are  the  last  to  succumb. 


GLOBULINS   AND   PEPTONES    AS    LOCAL    POISONS.  51 


CHAPTER    VI. 

THE  GLOBULINS  AND  PEPTONES  COMPARED  AS  REGARDS  LOCAL 

POISONOUS  ACTIVITY. 

IT  seems  needful  at  this  place  to  consider  the  relative  local  toxic  capacity  of 
globulins  and  peptones,  the  two  substances  found  in  varying  quantities  in  all  venoms 
as  yet  examined. 

In  order  to  do  this  effectively  it  will  be  needful  at  the  risk  of  anticipating  a  part 
of  what  belongs  strictly  speaking  to  the  pathological  section,  to  speak  briefly  of 
the  macroscopical  lesions  brought  about  at  the  seat  of  injection  by  these  potent 
substances. 

What  takes  place  intensely  where  the  injection  needle  enters,  but  represents  in 
a  violent  and  coarser  manner  lesions  to  be  found  soon  or  late  throughout  the 
body,  and  this  especially  applies  to  entire  venom  and  to  the  globulins.  These 
studies  of  local  changes  are  not  without  definite  explanatory  value.  It  has  long 
since  been  shown  that  the  cobra  and  the  rattlesnake  are  distinctive  poisoners,  and 
now  our  latest  work  seems  to  explain  just  why  this  is  so,  and  enables  us  to  see 
already  that  what  might  efficiently  aid  one  bitten  by  the  Indian  serpent,  would  be 
by  no  means  sure  to  succor  the  victim  of  our  own  less  fatal  snake. 

Venom  Peptones,  Local  Action. — The  albuminous  elements  of  venoms  are,  as 
already  shown,  two  in  number,  and  belong  by  virtue  of  their  reactions  respectively  to 
the  classes,  peptone  and  globulin.  Hence,  as  we  now  see  with  clearness,  it  is  easy  to 
separate  them  by  boiling,  irJtich  if  brief,  destroys  the  globulin  as  a  poison  and  leaves 
the  peptone  unaltered.  When  after  boiling  we  inject  the  fluid  and  coagula,  we 
still  poison,  if  the  dose  be  large,  for  the  venom  peptone  is  toxically  unchanged.  The 
wound  shows,  however,  hardly  any  of  the  singular  appearances  which  characterize 
lesions  due  to  fresh  or  unboiled  venom.  Boiling  leaves  the  poison  less  active 
locally.  If  continued  it  also  affects  more  or  less  the  general  toxicity,  but  this 
influence  is  most  marked  in  the  Crotaline  venoms,  hecause  in  them  the  peptone  is 
least  in  amount  and  is  also  the  least  deadly  of  the  two  constituent  poisons. 

Venom  Peptone. — When  venom  peptone  in  full  dose  is  injected  into  the  breast  of 
a  pigeon,  if  the  animal  dies  within  an  hour  or  two,  there  is  scarcely  any  appreci- 
able local  effect,  as  will  be  clearly  seen  by  examining  the  results  of  experiments 
recorded  in  the  chapter  on  the  influence  of  various  agents  on  the  poisonous  activity 
of  venom.  If  the  dose  be  smaller,  so  that  life  is  prolonged,  the  first  local  effect 
observed  is  a  considerable  cedematous  swelling  without  any  dark  discoloration. 
After  the  lapse  of  about  eighteen  hours  there  is  apt  to  be  some  discoloration,  and 
generally  a  discharge  of  muddy  putrescent  serum.  If  the  animal  be  killed  after  a 


52  THE    A'ENOMS    OF    CERTAIN    T  H  A  N  A  T  O  P  II I  D  E  JE. 

day  it  will  be  found  that  the  muscles  on  the  injected  side  about  the  region  of  the 
oedema  are  pale  and  bloodless,  having  the  appearance  of  half-cooked  chicken  meat. 
In  animals  which  lived  longer  there  was  sometimes  found  considerable  congestion, 
marked  by  greenish  streaks,  and  giving  oif  horrible  putrefactive  odors.  In  others 
beneath  the  ocdematous  swelling  lay  a  cavity  about  an  inch  in  diameter,  which 
was  full  of  broken-down  tissue,  having  a  muddy,  gangrenous  appearance,  and 
decidedly  putrescent,  while  the  surrounding  muscular  tissues  were  not  apparently 
altered  in  appearance.  In  none  of  these  experiments  were  ecchymoses  found  in 
the  intestines,  and  in  all  of  them  the  blood  was  coagulable. 

In  the  following  experiment  Crotalus  peptone  obtained  by  dialysis  was  at  2:37 
injected  into  the  breast  of  a  pigeon;  3:15  weak;  3:50  rocking  slightly,  no  local 
discoloration,  some  slight  oedematous  swelling ;  4:00  more  unsteady  on  its  feet ; 
5:45  there  was  considerable  watery  effusion  in  the  subcutaneous  cellular  tissue  on 
the  side  of  the  injection.  The  following  afternoon  there  was  a  large  swelling 
over  the  site  of  the  wound.  It  was  an  inch  or  more  above  the  healthy  skin, 
and  was  apparently  purely  oedematous  in  character,  there  being  no  dark  discolora- 
tion nor  appearances  of  congestion.  The  superficial  local  effect  was  in  every  way 
unlike  that  produced  by  the  globulins.  The  following  afternoon  (after  48  hours) 
the  pigeon  died.  The  swelling  was  unaltered  as  to  size,  and  but  very  little 
discolored.  The  tissues  around  it  were  slightly  darkened,  the  coloration  fading 
away  gradually  at  about  one-half  inch  from  the  border,  and  there  was  a  well-defined 
pale  streak  of  tissue  between  the  swelling  and  the  surrounding  tissue  like  a  line  of 
demarcation.  Upon  cutting  into  the  tumor  serum  dropped  from  the  incision,  and 
the  subcutaneous  cellular  tissue  was  found  greatly  infiltrated.  The  swelling  seemed 
to  be  almost  entirely  oedematous  and  the  serum  had  a  putrefactive  odor.  The  mus- 
cular tissues  were  greatly  congested  and  somewhat  blackened,  and  in  places  as  green 
as  though  infiltrated  with  bile.  This  green  appearance  could  be  seen  distinctly 
through  the  skin  on  the  surface  of  the  superficial  muscles,  extending  over  the 
entire  side  of  the  breast.  The  odor  emanating  from  the  cut  muscles  was  also  putre- 
factive. In  the  intermuscular  tissues  there  was  some  greenish  gelatinous  matter. 
Beneath  the  swelling  was  a  streak  of  muscular  tissue  about  one-fourth  of  an  inch 
thick,  which  was  very  pale,  like  half-stewed  meat,  contrasting  strongly  with  the 
other  parts  of  the  muscles. 

All  of  these  observations  on  slow  poisoning  were  made  with  peptone  derived 
from  the  venoms  of  the  Crotalus  adamantem  or  the  Moccasin. 

Judging  from  the  fact  that  the  venom  peptone  does  not  give  rise  to  any  darken- 
ing of  the  muscular  tissues  within  a  short  time  after  injection,  and  indeed,  as  it 
seems  probable,  not  until  putrefaction  has  set  in,  it  is  likely  that  the  darkening 
and  congestion  which  ultimately  occur  are  to  be  regarded  as  mere  secondary 
effects,  and  due  to  putrefactive  changes  induced  by  the  poison. 

The  peptones,  whether  obtained  by  boiling  or  dialysis,  seem  to  cause  locally  an 
enormous  oedema,  gradual  breaking  down  of  the  tissues,  and  rapid  production  of 
horrible  putrefactive  processes,  with  finally  a  more  or  less  extensive  slough.  They 
possess  little  power  to  produce  large  hemorrhages,  because  they  do  not  so  well  as 
venom  globulin  destroy  the  coagulability  of  the  blood.  Hence  in  peptone 


GLOBULINS   AND   PEPTONES   AS   LOCAL   POISONS.  53 

wounds  there  are  only  such  local  bleedings  as  are  due  to  the  leakage  caused  by 
gangrenous  processes.  The  ragged,  sodden  grayish  look  of  the  muscles  is  very 
remarkable,  and  once  seen  is  too  unfamiliar  not  to  be  remembered  as  a  most 
striking  pathological  appearance.  For  effects  of  peptone,  see  Plate  I. 

Venom  Globulins.  Local  Influence. — When  we  inject  unboiled  venom,  we  are 
using  globulin  as  well  as  peptone,  in  amounts  which  differ  with  every  serpent.  If 
we  use  the  isolated  globulins  the  contrast  in  the  local  phenomena  as  compared  with 
those  caused  by  peptones  is  immense.  The  different  globulins  already  described 
were  all  examined  in  this  connection. 

As  the  globulins  are  insoluble  in  water  free  from  salines,  dialysis  kept  up  long 
enough,  as  from  forty-eight  to  seventy-two  hours,  in  a  temperature  so  low  as  to 
insure  absence  of  putrefaction,  will  throw  down  the  mass  of  the  globulins  in  a 
form  which  enables  us  to  collect  and  re-dissolve  them.  Three  drops  of  Moccasin 
venom  were  mixed  with  6  c.  c.  distilled  water  and  dialysed  by  a  current  of  pure 
water  for  fifty-six  hours.  As  the  salts  passed  out  a  precipitate  increased  within 
the  dialyser.  After  having  been  washed  with  distilled  water,  it  was  thrown  into 
the  breast  of  a  pigeon.  Death  took  place  in  twenty-four  hours.  This  delay  in  a 
fatal  result  was  owing  to  the  dose  being  small,  and  perhaps  also  to  the  fact  that  it 
did  not  represent  all  the  globulin  of  three  drops  of  venom ;  after  death  there  was 
a  tense  black  swelling  at  the  site  of  the  wound,,  and  the  tissues,  for  two  inches 
in  every  direction,  were  soaked  with  black  absolutely  fluid  blood. 

It  is  difficult  to  subject  venom  constituents  to  any  processes  like  solution  or  dry- 
ing without  more  or  less  altering  their  toxicity.  Desiccation  certainly  affects  whole 
venom,  and  in  a  measure  lessens  the  severity  of  its  local  symptoms.  The  same  is 
true  of  venom  globulins.  An  equal  dose  of  globulin  dried  and  redissolved  takes 
longer  to  kill,  than  if  not  previously  dried ;  also  if  the  dried  venom  be  given  in 
unusual  dose,  the  local  effects  are  slighter  than  those  seen  with  pure  venom  or 
fresh  globulin  in  smaller  dose,  but  killing  within  the  same  time.  A  long  survival 
of  course  enables  the  local  phenomena  to  develop  and  might  mislead  as  to  the  fact 
of  drying  having  an  enfeebling  influence.  Desiccation  greatly  lessens  the  solubility 
of  venom,  and  of  its  albuminous  constituents,  and  in  consequence  they  fail  to 
permeate  the  tissues  and  to  enter  the  blood  at  the  rate  which  characterizes  fresh 
venom. 

In  the  experiment  which  follows,  death  was  long  delayed,  and  owing  to  this  the 
local  results  were  strongly  marked. 

A  quantity  of  globulin  obtained  by  dialysis,  representing  two  grains  of  the  venom 
of  the  Crotalus  adamanteus,  was  allowed  to  dry.  It  was  then  placed  in  a  little 
distilled  water,  and  after  a  few  minutes  a  small  amount  of  common  salt  was  added, 
which  caused  the  venom  and  water  to  form  a  milky  solution. 

This  was  injected  into  the  breast  muscles  of  a  pigeon  at  3:25;  3:40  some  darken- 
ing and  swelling  of  the  side  of  injection;  4:25  unable  to  stand;  6:00  convulsions, 
followed  by  death. 

Autopsy. — The  local  effect  of  the  venom  was  remarkable ;  beneath  the  skin  in  the 
areolar  tissue,  over  the  wounded  side  and  over  half  the  breast  of  the  opposite  side, 
was  a  mass  of  bloody  gelatinous  effusion,  and  the  muscles  beneath  on  the  injected 


54  THE   VENOMS   OF   CERTAIN   THANATOPHIDE^E. 

side  were  swollen  and  darkened  and  enormously  infiltrated  with  blood.     See  Plate 

II.,  Fig.  1. 

These  experiments,  which  have  been  supplemented  by  many  others,  give  a  some- 
what definite  idea  of  the  marked  difference  in  the  local  effects  of  the  globulins  as 
a  group  in  comparison  with  those  produced  by  the  boiled  solution  of  venom,  or 
in  other  words  by  the  venom  peptone. 

Experiment. — The  water-venom-globulin  from  0.03  gram  of  dried  venom  of  the 
Crotalus  adamanteus,  dissolved  in  a  little  water  by  means  of  a  few  crystals  of  salt, 
was  injected  into  the  breast  muscles  of  a  pigeon  at  3:55.  At  5:50  the  animal  was 
dead.  The  region  of  injection  was  terribly  swollen,  blackened,  and  suffused 
with  liquid  blood.  (The  amount  of  globulin  injected  was  about  0.003  gram.) 

In  a  rabbit  to  which  had  been  given  some  of  the  water-venom-globulin  intra- 
venously, enormous  extravasations  were  found  when  the  abdominal  cavity  was 
opened. 

In  another  experiment  with  the  water-venom-globulin  obtained  from  the  venom 
of  the  Moccasin,  the  animal  lived  for  some  time,  and  very  characteristic  effects  of 
slow  poisoning  from  venom  globulin  were  observed. 

Experiment. — One  c.  c.  of  distilled  water  containing  0.001  gram  of  water- 
venom-globulin  from  the  Moccasin  was  thrown  into  the  breast  muscles  of  a 
pigeon  at  5:26.  At  6:00  the  local  darkening  and  swelling  of  the  tissues  at  the 
region  of  injection  were  noticeable.  After  twenty-four  hours  the  animal  was  in  a 
generally  fair  condition  ;  the  side  was  considerably  darkened,  and  on  the  breast  was  a 
large  swelling,  which  appeared  to  be  due  to  a  bloody  effusion  into  the  subcutaneous 
tissue.  After  forty-eight  hours  there  was  a  discharge  of  red  serum  with  a  putre- 
factive odor.  The  whole  of  the  side  was  darkened  and  greenish,  and  had  the 
appearance  of  commencing  gangrene. 

Capper-venom-globulin. — Some  of  the  copper-venom-globulin  from  the  venom  of 
the  Crotalus  adamanteus  was  injected  with  a  little  water  into  the  breast  muscles  of 
a  pigeon  at  4:35.  At  5:00  it  was  weak,  but  no  local  effects  were  apparent.  On 
the  following  morning  it  was  dead.  The  local  effects  were  intense;  there  was 
considerable  swelling,  blackening,  and  diffusion  of  fluid  blood.  The  heart  was 
arrested  midway  between  systole  and  diastole,  and  contained  fluid  blood  of  a  dark 
color. 

Dialysis-venom-glolmlin. — Some  of  the  dialysis-venom-glolmlin  from  the  venom 
of  the  Crotalns  adamanteus  was  injected  into  the  breast  muscles  of  a  pigeon  at  5:03. 
At  5:18  was  sickish ;  5:19  unsteady,  side  somewhat  swollen  and  darkened;  5:30 
local  effect  increased.  Following  morning — dead.  Local  effects  intense — great 
swelling,  blackening,  and  diffusion  of  blood,  which  is  incoagulable. 

In  another  experiment,  in  which  a  larger  quantity  was  used,  the  bird  died  in 
twenty-five  minutes,  after  the  occurrence  of  stupor,  incoordination,  deep  laborious 
breathing,  and  convulsions.  There  was  no  time  for  very  decided  local  effects,  but 
the  blood  was  tarry  and  incoagulable. 

These  experiments,  which  have  been  frequently  repeated,  render  it  clear  that 
the  remarkable  local  effects  produced  by  the  venoms  of  the  Crotalus  and  Moccasin, 
and  which  are  not  observed  after  the  venom  is  boiled,  are  due  to  the  venom 


GLOBULINS   AND    PEPTONES    AS    LOCAL    POISONS.  55 

globulins,  all  of  which  bring  about  essentially  the  same  local  alterations.  To 
fully  satisfy  ourselves  that  these  interesting  local  effects  were  dependent  upon 
the  physiological  activities  of  the  globulins  and  not  upon  a  possible  contamination 
by  peptone,  observations  were  made  with  the  lolled  globulins.  In  none  were 
there  the  least  evidences  of  the  presence  of  any  poisonous  element. 

Whevever  globulins  alone  are  used,  we  have  these  local  bleedings,  fluid  blood, 
and  capillaries  giving  way  soon  after  the  poison  reaches  them.  The  system  at 
large  soon  or  late  repeats  the  coarser  phenomena  of  the  wound ;  and  yielding 
vessel  walls,  fluid  blood,  and  countless  hetnorrhagic  outflows  exhibit  the  power  of 
the  globulins.  Peptone,  or,  which  is  much  the  same,  briefly-boiled  venom,  causes 
putrefactive  changes  swiftly,  and  shows  but  slight  capacity  to  make  fluid  the  blood, 
or  to  corrode  the  capillaries.  The  wound  is  foul  and  cedematous,  but  not  filled 
with  blood,  whilst  in  its  general  effects  the  venom  peptone  fails  again  to  exhibit 
the  capacity  of  the  globulins  to  multiply  hemorrhages,  and  to  destroy  the  natural 
ability  of  the  blood  by  clotting  to  check  its  own  wasteful  expenditure. 

In  proportion  as  the  peptones  predominate  will  we  have  then  a  lessening  of 
rapidly  formed  local  lesions,  and  this  is  of  course  why  Cobra  venom  does  not  give 
us  the  same  terrible  local  consequences  which  ensue  in  Vaboia,  Moccasin,  and 
Crofalns  bites,  where  we  have  the  potent  combination  of  enough  peptones  and  an 
excess  of  globulins.  For  a  comparison  of  the  local  effects  of  Cobra  and  Crotalus 
poisoning,  see  Plate  II.,  Figs.  2  and  3. 


56       THE  VENOMS  OF  CERTAIN  T  H  A  N  A  T  0  PH  I  D  E  M. 


CHAPTER    VII. 

THE  ACTION  OF  VENOMS  AJXD  THEIR  ISOLATED  GLOBULINS  AND 
PEPTONES  UPON  THE  PULSE-RATE. 

SECTION  I. — PURE  VENOM. 

THE  experiments  made  in  connection  with  the  pulse-rate  were  performed  upon 
rabbits,  and  in  every  case,  unless  otherwise  noted,  the  poison  was  dissolved  in  1 
c.  c.  of  distilled  water  and  injected  intravenously,  usually  into  the  external  jugular 
vein. 

In  researches  made  with  the  isolated  poisons  doses  were  usually  employed 
which  represented  the  amount  of  the  individual  poison  contained  in  the  commonly 
employed  doses  of  the  pure  dried  venom,  thus  giving  a  fair  idea  of  the  part  played 
by  the  individual  principles  in  the  results  produced.  In  some  experiments,  how- 
ever, much  larger  doses  were  used  to  learn  more  fully  the  poisonous  character 
of  these  substances. 

In  all  of  our  observations  we  find  that  the  results  produced  in  animals,  under 
apparently  the  same  conditions  and  by  using  the  same  doses,  vary  very  greatly; 
sometimes  the  pulse  is  quickened  from  the  first  and  remains  beyond  the  normal 
until  death  ensues,  sometimes  there  is  a  primary  diminution  followed  by  an 
increase,  at  others  there  is  a  diminution  which  continues  until  death.  The  pulse 
is  generally  found  to  vary  much  in  frequency.  These  facts  all  suggest  that  the 
action  of  the  pure  venom  is  of  a  complex  nature;  there  being  several  factors  con- 
cerned in  the  various  alterations,  and  render  it  not  improbable  that  in  some  instances 
ecchymoses  in  the  various  organs  may  account  for  exceptional  variations. 

Twenty  experiments  were  made  with  pure  venoms  upon  normal  animals ;  six  of 
these  were  made  with  the  venom  of  the  Crotalus  adainanteus ;  in  three  the  pulse- 
rate  was  diminished  and  remained  below  normal,  in  two  there  was  a  primary 
increase  followed  by  a  diminution,  and  in  one  of  these  the  pulse-rate  afterwards  went 
above  the  normal,  while  in  another  there  was  a  primary  diminution  followed  by  an 
increase.  Of  two  experiments  made  with  the  Crotalus  Jiorridvs,  in  one  there  was 
an  increase  which  continued  until  death,  and  in  the  other  an  increase  followed  by 
a  diminution  below  the  normal,  this  diminution  in  turn  being  followed  by  a  rise 
above  the  normal,  which  continued  until  approaching  death.  In  two  experiments 
with  the  Ancistrodan  plscirorux,  in  one  there  was  an  increase  and  in  the  other  a 
decrease.  One  experiment  with  the  Andstrodon  contortrix  gave  an  increase.  In 
one  experiment  with  the  Crotalophorus  miliaris  there  was  a  decrease  followed  by 
an  increase.  In  one  with  the  Daboia  KmseUii,  which  was  not  a  perfectly  satis- 


THE  ACTION  OF  VENOMS  UPON  THE  PULSE-RATE. 


57 


factory  experiment,  there  was  a  decrease,  and  in  six  experiments  with  the  Cobra 
there  was  an  increase  in  all,  the  increase  being  followed  in  three  by  a  permanent 
decrease;  in  one  the  increase  was  followed  by  a  diminution,  and  this  in  turn  by  an 
increase;  in  two  experiments  there  was  a  permanent  increase,  excepting  near  death 
when  a  decrease  ensued. 

It  will  thus  be  clear  that  even  under  apparently  the  same  conditions  we  cannot 
foretell  what  the  alterations  in  the  pulse-rate  will  be  in  any  given  experiment ; 
although  the  results  of  the  six  experiments  with  Cobra  venom  are  so  uniform  in 
regard  to  the  primary  increase  as  to  indicate  that  with  it  at  least  we  should  always 
expect  to  find  more  or  less  acceleration  which  may  or  may  not  continue  above 
normal,  even  up  to  the  time  of  death. 

We  may  also  add  here,  that  we  cannot  trace  any  relations  in  the  alterations  in 
the  pulse,  arterial  pressure,  and  respiration  to  each  other,  so  that  it  seems  as  if 
the  changes  must  depend  essentially  upon  actions  peculiar  to  each  apparatus. 
This  holds  good  with  the  study  of  the  pure  venoms  or  their  isolated  poisons. 

Action  of  the  Pure  Venoms  upon  the  Pulse-rate  in  Normal  Animals. 
Experiment  No.  1. 


Normal 


Time  : 

Pulsations 

mill. 

sec. 

per  minute. 

. 

285 

20 

285 

40 

285 

1 

00 

285 

1 

20 

285 

] 

40 

285 

2 

00 

? 

5 

00 

285 

7 

00 

285 

8 

00 

285 

9 

00 

270 

10 

00 

270 

11 

00 

240 

1-2 

00 

255 

13 

00 

270 

20 

00 

270 

21 

30 

270 

23 

00 

270 

REMARKS. 


Experiment  No.  2. 


Normal 


Time: 
niin.   sec. 

20 
40 

1     00 
1     20 

April,  1886. 


Pulsations 
per  minute. 

240 
240 
240 
195 


Injected  1  drop  of  fresh  venom  from  the  Crolalus  adamanteus 
into  the  thigh  of  a  large  rabbit. 


Clot  in  canula. 


At  1:00  the  blood-pressure  began  falling  and  reached  a 
minimum  at  10:00,  when  it  was  one-third  less  than  the 
normal. 


REMARKS. 

Injected  3  drops  of  the  fresh  venom  of  the  Crotalus  adaman- 
teus into  the  thigh  of  a  large  rabbit. 


Animal  broke  loose  and  tore  the  canula  from  the  artery. 


58 


THE    VENOMS   OF    CERTAIN    T  II A  N  A  T  0  P  HI  D  E  M. 


Eaoperiment 

No.  3. 

Time  : 

Pulsations 

uiiii.   sec. 

per  minute. 

Normal 

... 

255 

10 

240 

20 

225 

30 

225 

40 

210 

50 

195 

1     00 

195 

1     20 

210 

1     40 

210 

2     00 

225 

2     20 

270 

2     40 

270 

Experiment  No.  4. 

Time: 

Pulsations 

uiiii.   sec. 

per  minute. 

Normal 

.   .    . 

300 

5 

310 

10 

330 

20 

330 

30 

300 

40 

270 

50 

270 

1     00 

270 

1     20 

280 

1     40 

270 

2     10 

270 

4     00 

280 

7     00 

300 

8     00 

90 

8     10 

130 

8     20 

170 

8     30 

240 

8     40 

292 

8     50 

320 

10     30 

320 

13     00 

280 

13     30 

.    .    . 

13     50  ' 

300 

14     00 

300 

16     00 

280 

16     05 

... 

16     30 

280 

17     00 

•    *    * 

REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cro- 
talus  adainanteua  ill  1  c.  c.  distilled  water. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cro- 
talus  adamanteus  dissolved  in  1  c.  c.  distilled  water. 


Struggles  accompanied  by  remarkably  slow  heart  beats  and 
considerable  increase  of  arterial  pressure. 


Injected  0.003  gram  dried  venom  dissolved  in  1  c.  c.  distilled 
water. 


Repeated  the  injection. 

Dead.    Heart  in  complete  diastole;  blood  incoagulable,  ecchy- 
moses  in  pericardium  and  peritoneum. 


THE  ACTION  OF  VENOMS  UPON  THE  PULSE -RATE. 


59 


Experiment  No.  5. 

Time  : 

Pulsations 

min.   sec. 

per  minute. 

Normal          .  .  . 

225 

10 

270 

20 

120 

30 

180 

40 

285 

1     00 

285 

1     20 

285 

1     40 

285 

2     00 

285 

4     00 

? 

8     00 

Experiment  No.  6. 

Time  : 

Pulsatfons 

min.  sec. 

per  minute. 

Normal          .  .  . 

323 

5 

315 

20 

214 

30 

225 

40 

255 

1     00 

255 

1     30 

255 

3     30 

240 

5     30 

240 

7     30 

225 

8     00 

195 

13     00 

195 

17     30 

Experiment  No.  7. 

Time: 

Pulsations 

min.  sec. 

per  minute. 

Normal          .  .  . 

260 

5 

260 

20 

98 

30 

84 

40 

120 

1     00 

Experiment  No.  8. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal          .  .  . 

300 

10 

195 

30 

60 

44 

70 

55 

130 

60 

220 

80 

260 

1     40 

REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 
lalus  adamanleus  dissolved  in  1  c.  c.  distilled  water. 


I  Struggles. 


Too  feeble  to  count. 
Dead. 


REMARKS. 


Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 
talus  adamanleus  dissolved  in  1  c.  c.  distilled  water. 


Dead. 


REMARKS. 

Injected  intravenously  0.02  gram  dried  venom  of  the  Crotalus 

adamanleus  dissolved  in  1  c.  c.  distilled  water. 
Blood  pressure  increased,  probably  due  to  asphyxia. 


Dead. 


REMARKS. 

Injected  into  the  right  carotid  artery  0.015  gram  dried  venom 
of  the  Crolalus  adamanleus  dissolved  in  1  c.  c.  distilled 
water. 


Dead. 


60 


THE  VENOMS  OF  CERTAIN  THAN A TO PHI 


Experiment  No.  9. 


Time  : 

Pulsations 

REMARKS. 

Normal 

mill.    see. 

10 

per  minute. 

225 
235 

Injected  intravenously  0.015  gram  dried  venom  of  the 
talus  horridus  dissolved  in  1  c.  c.  distilled  water. 

Cro- 

20 

240 

30 

240 

50 

240 

1     00 

240 

1     10 

240 

1     20 

240 

1     30 

240 

1     40 

240 

3     40 

260 

5     40 

280 

7     40 

330 

9     40 

350 

Convulsions. 

10     10 

Dead. 

Experiment  No.  10. 

Normal 

Time: 
min.   sec. 

5 

Pulsations 
per  minute. 

270 

REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the 
talus  horridus  dissolved  in  1  c.  c.  distilled  water. 

Cro- 

10 

.    .    . 

20 

... 

30 
2     40 

370 

Animal   broke  loose  and  was  replaced  —  record   before 
time  valueless. 

this 

3     00 

400 

5     00 

350 

6     30 

225 

x 

7     30 

240 

8     00 

280 

8     30 

280 

9     00 

330 

10     00 

90 

Respirations  cease. 

Experiment  No.  11.                         , 

Normal 

Time: 
min.   sec. 

20 
30 

Pulsations 
per  minute. 

216 
228 
228 

REMARKS. 

Injected  intravenously  0.004  pram  dried  venom  of  the  Ancis- 
trodon  piscivorus  dissolved  in  1  c.  c.  distilled  water. 
Convulsions. 

40 

245 

1     00 

252 

1     30 

1     50 

240 
284 

Injected  a  similar  dose. 

2     10 

280 

2     30 

280 

3     00 

280 

4     00 

•    •    • 

Killed  by  pithing. 

THE  ACTION  OF  VENOMS  UPON  THE  PULSE-RATE. 


61 


Experiment 

No.  12. 

Time: 

Pulsations 

REMARKS. 

miu.    sec. 

Normal          .   .   . 
10 
20 

per  minute. 
305 
300 

240 

Injected  intravenously  0.004  gram  dried  venom  of  the  Ancis- 
trodon  piscivorus  dissolved  in  1  c.  c.  distilled  water. 

30 

240 

1      00 
1      30 

270 
265 

2      00 

265 

2     30 

270 

3     00 

275 

5     00 

300 

5     30 
5     35 

300 
300 

Injected  as  in  the  foregoing. 

5     45 

300 

6     05 

260 

6     15 
6     25 

I  Convulsive  movements 

6     45 

250 

7     25 

145 

7     35 

130 

7     45 

120 

7     55 

100 

8     05 

115 

8     15 

120 

8     25 

132 

Animal  died  in  a  few  minutes. 

Experiment 

No.  13. 

Time: 

Pulsations 

REMARKS. 

min.    sec. 

Normal          .   .  . 
10 

per  minute. 

320 
320 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 
trodon  conlortrix  dissolved  iii  1  c.  c.  distilled  water. 

30 

370 

1     00 

340 

1     30 

340 

2     00 

330 

2     30 

330 

4     30 

360 

5     30 
5     50 
6     30 

350 
320 
250 

Injected  as  in  the  foregoing. 
Struggles. 

6     50 

360 

7     50 
10     00 

390 

Injection  repeated. 
Death. 

THE   VENOMS   OF    CERTAIN    Til  A  N  A  T  0  P  H  I  D  E  JE. 


Experiment  No.  14. 


Time: 

Pulsations 

REMARKS. 

min.   sec. 

per  miuute. 

Normal 

.    .    . 

280 

Injected  intravenously  0.003  gram  dried  venom  of  the  Crota- 

20 

285 

lophorus  miliaris  dissolved  iu  1  c.  c.  distilled  water. 

30 

128 

40' 

135 

50 

240 

Struggles. 

1     00 

285 

1     10 

285 

2     10 

290 

2     40 

300 

Injected  0.006  gram. 

2     50 

300 

3     20 

250 

5     20 

275 

7     20 

300 

9     20 

315 

* 

Experiment  No.  15. 

Time: 

Pulsations 

REMARKS. 

min.  sec. 

per  minute. 

Normal 

... 

240 

Injected  intravenously  0.003  gram  dried  Cobra  venom 

dis- 

10 

240 

solved  iu  1  c.  c.  distilled  water. 

30 

250 

1     00 

260 

1     20 

250 

3     20 

250 

5     20 

260 

Experiment  No.  16. 

Time: 

Pulsations 

REMARKS. 

min.   sec. 

per  minute. 

Normal 

205 

Injected  intravenously  0.003  gram  dried  Cobra  venom  dis- 

1    00 

205 

solved  in  1  c.  c.  distilled  water  with  a  few  crystals  of 

sodic 

3     00 

203 

chloride. 

8     00 

205 

10     00 

126 

15     00 

105 

17     00 

105 

19     00 

Dead. 

Experiment  No.  17. 

Time: 

Pulsations 

REMARKS. 

min.   sec. 

per  minute. 

Normal 

.    .    . 

260 

Injected  intravenously  0.005  gram  dried  Cobra  venom 

dis- 

20 

270 

solved  in  1  c.  c.  distilled  water  with  a  few  crystals  of 

sodic 

30 

250 

chloride. 

40 

250 

1     00 

250 

1     20 

250 

1     40 

230 

4     40 

240 

7     40 

250 

8     40 

190 

9     10 

.    .    . 

Clot  in  canula. 

15     00 

•    .    . 

Dead. 

THE  ACTION  OF  VENOMS  UPON  THE  PULSE-KATE. 


63 


Experiment  No.  18. 


Time  : 

Pulsations 

min.   sec. 

PIT  iiiiniiti'. 

Normal 

.    .    . 

310 

10 

310 

20 

320 

30 

310 

40 

200 

1     00 

310 

1     30 

330 

2     00 

340 

2     10 

340 

6     20 

150 

6     50 

150 

1     30 

165 

8     20 

Experiment  No.  19. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    . 

290 

10 

290 

15 

280 

20 

280 

30 

280 

40 

2     00 

Experiment  No.  20. 

Time: 

Pulsations. 

min.   sec. 

per  minute. 

Normai 

.    .    . 

216 

0 

13 

20 

252 

40 

252 

1     00 

264 

1     30 

288 

2     00 

260 

4     00 

264 

9     00 

231 

12     00 

108 

14     00 

48 

20 

126 

REMARKS. 

Injected  intravenously  0.015  gram  dried  Cobra  venom  dis- 
solved in  1  c.  e.  distilled  water. 


Dead. 


REMARKS. 

Injected  intravenously  0.005  gram  dried  venom  of  the  Daboia 
Jiussellii  dissolved  in  0.5  c.  c.  distilled  water. 


Tetanic  convulsions. 
Dead. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cobra 
dissolved  in  1  c.  c.  distilled  water. 


Respiration  ceased ;  artificial  respiration  used. 


Actions  of  Pure  Venoms  on  the  Pulse-rate  in  Animals  with  Cut  Pneumogastric 
Nerves. — After  section  of  the  pneumogastric  nerves  we  invariably  found  an  increase 
which  was,  as  a  rule,  very  slight.  Seven  experiments  in  all  were  made  on  animals 
thus  operated  upon:  one  with  the  venom  of  the  Crotalns  adamanteus  ;  one  with 
the  Crotalns  horridus  ;  one  with  the  Ancistrodon  piscivorus  ;  one  with  the  Ancis- 
trodon  contort rix,  and  three  with  the  Cobra. 


THE    VENOMS   OF    CERTAIN    T  II  A  N  A  T  0  I'  II 1  D  E  .E. 


Experiment  No.  21. 

Time  : 

Pulsations 

min.   sec. 

per  minute. 

Normal          .  .   . 

295 

10 

300 

30 

300 

1     00 

300 

1     30 

295 

2     00 

300 

2     30 

305 

5     30 

290 

1     00 

285 

8     30 

.  .  . 

9     30 

Experiment  No.  22. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal          .  .  . 

315 

20 

1     00 

320 

1     20 

335 

1     40 

330 

2     00 

320 

2     20 

340 

4     20 

340 

5     50 

350 

8 

Experiment  No.  23. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal          .  .   . 

240 

20 

300 

30 

300 

40 

300 

50 

300 

1     00 

240 

1     20 

225 

3     50 

210 

5     50 

270 

6     00 

300 

8     00 

285 

10     00 

270 

12     00 

270 

14     00 

285 

19     00 

240 

19     10 

255 

19     20 

255 

19     30 

255 

19     40 

240 

19     50 

240 

20     00 

240 

REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  0.003 
grain  dried  venom  of  the  Crotalus  adamanleus  dissolved 
in  1  c.  c.  distilled  water. 


Injected  a  similar  dose. 
Dead. 


REMARKS. 


Pneumogastric  nerves  cut.  Injected  intravenously  0.015 
gram  dried  venom  of  the  Crotalus  horridus  dissolved  in 
1  c.  c.  distilled  water. 

Violent  struggles. 


Dead. 


REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  0.003 
gram  dried  venom  of  the  Ancistrodon  piscivonts  dissolved 
in  1  c.  c.  distilled  water. 

Struggles. 


Struggles. 
Convulsions. 


Injected  a  similar  dose. 


THE  ACTION  OF  VENOMS  UPON  THE  PULSE-HATE. 


65 


Tinif  : 

Pulsations 

min.   eec. 

JK.T  minute. 

20     20 

240 

21     20 

255 

23     20 

300 

25     20 

270 

28     20 

255 

33     20 

255 

38     20 

255 

44     20 

255 

44     40 

225 

45     10 

Experiment  No.  24. 

Time  : 

Pulsations 

min.   see. 

per  minute. 

Normal 

.    .    . 

300 

10 

300 

20 

310 

30 

310 

40 

310 

1     00 

310 

1     50 

310 

4     20 

310 

7     00 

310 

7     05 

.    .    . 

1     10 

320 

T     20 

300 

7     40 

300 

8     00 

310 

9     00 

315 

11     30 

300 

11     40 

295 

12     00 

290 

12     30 

290 

13     00 

290 

13     30 

290 

19     00 

285 

19     20 

270 

19     40 

270 

20     20 

285 

21     50 

285 

22     50 

285 

Experiment  No.  25. 

Time  : 

Pulsations 

mm.   sec. 

per  minute. 

Normal 

.    .    . 

330 

10 

330 

30 

330 

1     00 

330 

3     30 

340 

6     30 

330 

10     30 

320 

14     30 

295 

16     30 

275 

REMARKS. 


Injected  a  similar  dose. 


Dead. 


REMARKS. 

Pneurnogastric  nerves  cut.  Injected  intravenously  0.003 
gram  dried  venom  of  the  Ancislrodon  conlortrix  dissolved 
in  1  c.  c.  distilled  water. 


Injected  a  similar  dose. 

Struggles. 


Injected  a  similar  dose. 


REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  0.003 
gram  dried  Cobra  venom  dissolved  in  1  c.  c.  distilled  water 
with  a  few  crystals  of  sodic  chloride  and  filtered. 


Clot  formed  in  canula. 


May,  1886. 


66 


THE    VENOMS    OF    CERTAIN    T H A N A T 0 P HI D E M. 


Experiment  No.  26. 

Time :  Pulsations                                                        REMARKS, 

min.   sec.  per  minute. 

Normal          .  .  .  320         Pneumogastric   nerves   cut.       Injected   intravenously  0.006 

10  sift             grain   dried  Cobra  venom   prepared  as    iu   the  foregoing 

30  330             experiment. 

1     00  330 

1     30  330 

3     30  335 

5     30  340 

9     30  320 

11     30  330 

18     30  ...         Convulsions;  asphyxia;  death  in  2^  minutes. 


Experiment  No.  27. 

Time :  Pulsations 

min.   sec.        per  minute. 


REMARKS. 


Normal 


0 
10 
20 

1  00 

2  00 
4     00 

10 
15 


390 


396 
390 
360 
354 


Pneumogastric   nerves    cut.      Injected    intravenously  0.003 
gram  dried  Cobra  veuoiu  dissolved  in  1  c.  c.  distilled  water. 


Clot  in  canula. 
Dead  of  asphyxia. 


The  Actions  of  Pure  Venoms  on  Animals  in  which  Sections  of  the  Pneitmor/astric 
Nerves  and  of  the  Upper  Cervical  Portion  of  the  Spinal  Cord  had  been  made. — 
After  isolation  of  the  heart  from  the  nerve  centres  by  making  section  of  the 
pneumogastric  nerves  and  spinal  cord  in  the  middle  or  upper  cervical  region,  and 
maintaining  the  animal  alive  by  means  of  artificial  respiration,  we  find  that  the 
pulsations  of  the  heart  are  almost  invariably  slightly  diminished  in  frequency 
upon  use  of  venom.  Seven  experiments  were  made:  three  with  the  venom  of  the 
Crotalus  adamanteus ;  one  with  the  Crotalus  horridus ;  one  with  the  Ancistrodon 
piscivorus ;  one  with  the  Ancistrodon  contortrix,  and  one  with  Cobra.  In  one  expe- 
riment with  the  Crotahts  adamanteus  in  which  two  doses  were  given,  there  occurred 
a  diminution  after  the  first  dose,  while  there  was  a  marked  increase  after  the  second. 
In  the  experiment  with  the  Crotalus  horridus  there  was  but  little  alteration. 


Experiment  No.  28. 


Normal 


Time: 

Pulsations 

min. 

sec. 

per  minute. 

. 

240 

10 

235 

20 

230 

30 

225 

40 

215 

1 

00 

210 

1 

20 

210 

1 

40 

210 

2 

40 

REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.003  gram  dried  venom  of  the  Crotalus  adamanteus  dis- 
solved in  1  c.  c.  distilled  water. 


Dead. 


THE    ACTION    OF    VENOMS    UPON   THE    PULSE-RATE. 


67 


Experiment 

No.  29. 

Time  : 

Pulsations 

iniii.   sec. 

per  minute. 

Normal 

.    .    . 

185 

10 

185 

20 

185 

30 

180 

1     00 

180 

1     20 

180 

3     20 

180 

3     50 

180 

5     50 

160 

7     50 

Experiment 

No.  30. 

Time  : 

Pulsations 

miu.   sec. 

per  minute. 

Normal 

240 

10 

230 

20 

230 

30 

230 

40 

195 

1     00 

200 

1     20 

205 

1     40 

210 

2     00 

230 

2     30 

265 

3     00 

250 

6     00 

300? 

6     05 

265 

6     15 

.    .    . 

6     35 

270 

1     05 

260 

7     35 

260 

8     05 

260 

15     05 

Experiment 

No.  31. 

Time  : 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    . 

235 

10 

230 

30 

240 

40 

240 

1     00 

235 

2     00 

240 

4     00 

240 

6     00 

230 

8     00 

220 

REMARKS. 

185  Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.(To:i  gi-iiin  dried  venom  of  the  Crotalus  adamanlcux  dis- 
solved in  1  c.  c.  distilled  water. 


Dead. 


REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.003  gram  dried  venom  of  the  Crotalus  adamanteus  dis- 
solved in  1  c.  c.  distilled  water. 


Injected  a  similar  dose. 


Dead. 


REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.015  gram  dried  venom  of  the  Crotalus  horridus  dis- 
solved in  1  c.  c.  distilled  water. 


12     00 


Dead. 


68 


THE   TENOMS   OF   CERTAIN    T  II  A  N  A  T  0  PH  ID  E  M. 


Experiment  No.  32. 


Time  : 

Pulsations 

miu.   sec. 

per  minute. 

Normal 

220 

20 

210 

30 

200 

40 

200 

1     00 

210 

1     30 

210 

1     50 

210 

4     20 

195 

8     20 

'210 

10     20 

210 

12     20 

210 

15     20 

210 

18     20 

210 

21     20 

Experiment  No.  33. 

Time: 

Pulsations 

mill.    66C. 

per  minute. 

Normal 

... 

260 

10 

255 

20 

250 

40 

243 

1     00 

243 

1     30 

245 

2     00 

240 

4     00 

240 

7     00 

240 

9     00 

240 

11     00 

240 

13     00 

240 

15     00 

240 

17     00 

240 

20     00 

240 

22     00 

240 

22     15 

? 

22     30 

? 

Experiment  No.  34. 

Time  : 

Pulsations 

rain.   sec. 

per  minute. 

Normal 

.    .    . 

220 

10 

215 

30 

215 

1     00 

210 

3     00 

215 

5     00 

215 

8     00 

225 

11     00 

225 

14     00 

225 

19     00 

225 

REMARKS. 

Pnenniogastric  nerves  and  cord  cut.  Injected  intravenously 
0.003  gram  cMed  venom  of  the  Ancistrodon  piscivurus 
dissolved  in  1  c.  c.  distilled  water. 

Struggles. 


Dead. 


REMARKS. 


Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.003  gram  dried  venom  of  the  Ancistrodon  contorlrix 
dissolved  in  1  c.  c.  distilled  water. 


Injected  0.006  gram. 


Dead. 


REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.003  gram  dried  Cobra  venom  dissolved  in  1  c.  c.  distilled 
water. 


Killed  by  pithing. 


THE  ACTION  OF  VENOMS  UPON  THE  PULSE-RATE.     69 

Summary  and  Conclusions  of  the  Actions  of  Venoms  on  the  Pulse-rate, — The 
results  of  this  series  of  experiments  indicate  that  the  primary  tendency  of  venoms 
is  to  cause  an  increase  of  the  pulse-rate,  that  this  tendency  is  greater  after  section 
of  the  pneumogastric  nerves,  and  that  it  rarely  occurs  after  conjoined  section  of 
the  pneumogastric  nerves  and  the  -upper  or  middle  cervical  region  of  the  spinal 
cord. 

From  the  increased  tendency  to  acceleration  of  the  pulse-rate  in  poisoning  by 
venom  after  section  of  the  pneumogastric  nerves  we  infer  that  there  is  some  direct 
or  indirect  effect  of  the  venom  upon  the  pneumogastric  centres  by  which  an  inhibi- 
tory influence  is  exerted,  and  which  tends  to  neutralize  the  action  bringing  about 
acceleration.  Since  hastening  of  the  pulse  is  a  rare  occurrence  after  conjoint 
section  of  the  pneumogastric  nerves  and  the  cervical  spinal  cord,  we  think  that 
the  increase  is  due  for  the  most  part  to  some  effect  upon  the  accelerator  centres 
in  the  medulla,  whereby  impulses  are  sent  through  (chiefly  at  least)  those  of  the 
accelerator  fibres  which  pass  by  the  cord.  The  increase  of  the  pulse-rate  which 
may  occur  after  division  of  the  nerves  distributed  to  the  heart,  by  section  of  the 
pneumogastric  nerves  and  cervical  spinal  cord,  must  be  dependent  upon  a  direct 
action  of  the  venom  upon  the  heart  muscle  or  its  contained  ganglia. 

The  diminution  in  the  heart  beats  must  be  due  to  a  direct  cardiac  action,  since 
it  occurs  after  isolation  of  the  heart,  as  above,  from  any  central  nervous  influence. 

In  these  as  in  all  other  experiments  which  involve  intravenous  use  of  venoms  we 
are  liable  to  disturbing  elements  which  do  not  trouble  our  explanations  in  dealing 
with  other  poisons.  At  any  moment,  anywhere  in  nerve-tissue  or  muscles,  we  may 
have  abrupt  and  quite  countless  hemorrhages.  How  these  may  introduce  con- 
flicting symptoms  and  modify  results  has  already  been  pointed  out  by  one  of  us 
many  years  ago.1  They  make  absolute  constancy  of  effects  quite  improbable. 


SECTION  II. — THE  ACTIONS  OF  GLOBULINS  ON  THE  PULSE-RATE. 

The  Actions  of  the  Venom  Globulins  on  the  Pulse-rate. — The  actions  of  the  venom 
globulins  upon  the  pulse-rate  appear  to  differ  somewhat  in  quality  from  what  is 
found  in  poisoning  with  pure  venoms;  there  is  a  greater  tendency  to  the  primary 
increase  in  the  pulse  than  with  pure  venoms,  while  the  action  by  which  this  is 
brought  about  seems  to  differ. 

Of  eleven  experiments  in  which  the  amounts  used  represented  the  proportion 
of  the  respective  globulins  contained  in  the  usual  doses  of  venom  given,  six  were 
made  with  the  water-venom-globulin,  two  with  the  copper-venom-globulin,  and  three 
with  the  dialysis-venom-globulin ;  all  of  these  poisons,  excepting  in  one  experiment 
with  the  water-venom-globulin  of  the  Ancistrodon,  were  derived  from  the  venom 
of  the  Crotalus  adamanteus. 

The  water-venom-globulin  seems  to  be  the  most  active,  and  the  copper-venom- 

1  Researches  on  the  Veuom  of  the  Rattlesnake.     S.  Weir  Mitchell,  1861. 


70 


THE    VENOMS   OF    CERTAIN    T H A N A T 0 P H I D E M. 


globulin  the  least  so.  Of  the  six  experiments  with  the  former,  in  four  there  was 
a  primary  increase  in  the  pulse-rate  followed  by  diminution,  and  in  one  case  by  a 
subsequent  increase;  in  the  other  two  there  was  a  diminution  from  the  first,  the 
pulse  regaining  its  normal  frequency,  or,  as  in  one  instance,  rising  above  it. 

In  both  the  experiments  with  copper-venom-globulin  there  was  a  primary  increase 
followed  by  a  diminution  in  one  case,  and  in  the  other  by  a  return  of  the  rate  to 
about  the  normal. 

In  the  three  experiments  with  dialysis-venom-globulin,  a  primary  increase  occur- 
red. In  two  this  was  followed  by  a  drop  below  normal,  while  in  the  other  the 
rate  remained  above  the  normal. 


Experiment  No.  35. 


Time  : 

Pulsations 

mill.   sec. 

per  minute. 

Normal 

.    .    . 

290 

10 

305 

20 

310 

40 

315 

1     00 

290 

1     30 

270 

3     00 

270 

5     00 

270 

7     00 

270 

9     00 

280 

12     00 

290 

15     00 

300 

18     00 

315 

25     00 

320 

35     00 

330 

45     00 

330 

55     00 

330 

Experiment  No.  36. 

Time  : 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    . 

310 

10 

310 

20 

275 

40 

265 

1     00 

260 

1     20 

260 

1     40 

280 

3     40 

290 

7     40 

310 

9     40 

310 

10     00 

315 

10     20 

300 

10     40 

300 

14     00 

300 

17     00 

300 

20     00 

300 

30     00 

300 

REMARKS. 

Injected  intravenously  0.0012  gram  watcr-venom-globulin 
(—  0.015  gram  dried  venom)  from  the  venom  of  the  Gro- 
talus  adamanteus. 


Killed. 


REMARKS. 


Injected  intravenously  the  water-venom-globulin  from  0.03 
gram  dried  venom  of  the  Crotalus  adamanteus. 


Clot  in  canula. 


Injected  water-venom-globulin  from  0.015  gram  dried  venom 


Killed  by  pithing. 


THE  ACTION  OF  VENOMS  UPON  THE  PULSE-RATE. 


Experiment  No.  37. 


Time  : 

Pulsations 

iiiin.   sec. 

per  minute. 

Normal 

320 

10 

350 

20 

330 

30 

305 

50 

300 

1      10 

300 

4     10 

300 

4     30 

310 

4     35 

310 

4     40 

310 

4     50 

310 

15 

Experiment  No.  38. 

Time: 

Pulsations 

iiiin.   sec. 

per  minute. 

Normal 

.    .    . 

270 

10 

290 

20 

295 

30 

295 

50 

260 

1     00 

255 

1     30 

260 

3     30 

265 

5     30 

260 

7     30 

265 

9     30 

265 

12     30 

260 

14     30 

260 

10     30 

270 

17     30 

275 

19     30 

275 

21     30 

260 

2G     00 

260 

28     00 

260 

30     00 

2fiO 

30     15 

260 

35     00 

260 

37     00 

260 

39     00 

255 

Experiment  No.  33. 

Time: 

Pulsations 

iiiin.   sec. 

per  minute. 

Normal 

280 

30 

270 

50 

230 

1     00 

220? 

1     30 

280 

1     50 

260 

2     00 

180 

2     40 

260 

- 

3     10 

280 

REMARKS. 


Injected  intravenously  0.0033  gram  water  -venom-globulin 
from  the  dried  venom  of  the  Crolalux  adamanleus  dissolved 
by  the  addition  of  a  trace  of  sodic  carbonate. 


Injected  double  dose. 


Injected  double  dose. 
Killed  by  pithing. 


REMARKS. 


Injected    intravenously  the  water-venom-globulin  from  one 
minim  of  fresh  venom  of  the  Crotalus  adamanleus. 


Clot  in  canula. 


Clot  in  canula. 


Animal  killed  by  pithing. 


REMARKS. 

Injected  intravenously  the  water-venom-globulin  from  0.004 
gram  dried  venom  of  the  Ancixtrodon  piscivorus  dissolved 
in  1  c.  c.  distilled  water  by  the  addition  of  a  few  crystals  of 
sodic  chloride. 

Injected  a  similar  dose. 


72       THE  VENOMS  OF  CERTAIN  TH  A  N  A  T  O  P  H  I  D  E 

Experiment  No.  40. 


Normal 


Time :  Pulsations  EEMARKS. 

min.   sec.        per  minute. 

...  312         Injected  intravenously  the  water-venom-globulin  from  0.015 

grain  dried  venom  of  the  Crotalus  adamanleus. 


0 

.  .  . 

10 

.1,1 

314 

^sU 

30 

360 

1 

30 

316 

2 

30 

304 

5 

30 

324 

10 

30 

354 

14 

30 

360 

19 

30 

396 

24 

30 

384 

29 

30 

372 

34 

30 

372 

42 

30 

372 

47 

30 

372 

52 

30 

372 

57 

30 

360 

67 

30 

316 

77 

30 

316 

80 

30 

120 

85 

*  .  • 

Normal 


Time : 
min.   sec. 

10 
20 
30 
50 

2  50 
4  50 
6  50 
8  50 

10  50 

11  50 

17  20 

18  20 
18  30 
18  40 

18  50 

19  00 

20  00 
22  00 
27  00 


Hsematuria. 


Dead;  ecchymoses  in  intestines;  blood  fluid. 


Experiment  No.  41. 


Pulsations  REMARKS, 

per  minute. 

280         Injected  intravenously  0.0012  gram  copper-ve.nom-globulin 

285  from  the  dried  venom  of  the  Crolalus  adamanteus. 

290 

285 

280 

270 

270 

260 

260 

255 

260 

280 

280 

300 

290 

285 

280 

285 

285 

290 


Injected  a  similar  dose. 


THE    ACTION    OF    VENOMS    UPON    THE    PULSE-RATE. 


Experiment  No.  42. 


Time: 

Pulsations 

mln.    sec. 

per  minute. 

Normal 

290 

10 

290 

30 

305 

1     00 

310 

3     00 

310 

5     00 

310 

7     00 

310 

8     00 

310 

10     00 

310 

12     00 

312 

22     00 

280 

24     00 

280 

26     00 

280 

20     10 

285 

26     20 

290 

26     30 

290 

27     00 

290 

27     00 

290 

29     00 

280 

31     00 

270 

34     00 

250 

39     00 

295 

41     00 

290 

43     00 

285 

45     00 

285 

52     00 

295 

58     00 

295 

Experiment  No.  43. 

Time: 

Pulsations 

niiu.   sec. 

per  minute. 

Normal 

290 

20 

365 

40 

305 

50 

305 

1     20 

295 

3     20 

275 

5     20 

275 

18     20 

280 

18     23 

.    .    . 

18     30 

290 

18     45 

280 

19     05 

19     25 

270 

19     55 

270 

20     25 

270 

21     25 

138 

22     00 

315 

30     00 

•    «    • 

10 

May,  1S86. 

KEMARKS. 

Injected  intravenously  0.00225  gram  copper-venom-globulin 
from  the  dried  venom  of  the  Crotalus  adamanteus. 


Clot  in  canula. 


Injected  0.0045  gram. 


REMARKS. 

Injected  intravenously  0.0017  gram  dialysis-venom-globvlin 
from  the  dried  venom  of  the  Crotalus  adamanteus  dissolved 
in  1  c.  c.  distilled  water  with  a  trace  of  sodic  carbonate. 


Animal  broke  loose. 

Injected  0.0034  gram  dialysis-venom-globulin. 

Struggles. 


Dead. 


74 


THE    VENOMS    OF    CERTAIN    T  H  A  N  A  T  0  I'll  I  D  E 


Experiment  No.  44. 


Time: 


Pulsations 


Normal 


min 

,  sec. 

per  minute. 

, 

.  . 

265 

20 

280 

30 

290 

i 

00 

270 

i 

20 

270 

i 

40 

270 

2 

00 

265 

2 

40 

280 

3 

40 

280 

5 

40 

285 

6 

20 

285 

6 

50 

285 

7 

20 

300 

7 

50 

300 

8 

50 

300 

9 

20 

300 

9 

50 

300 

10 

50 

300 

11 

50 

300 

12 

50 

300 

14 

20 

300 

REMARKS. 

Injected  intravenously  dialysis-venom-globulin  from  the  dried 
venom  of  the  Crotalus  adamanleus. 


Experiment  No.  45. 


Normal 


Time  : 
min.  sec. 


10 
20 
30 
00 
00 
00 
00 
00 
30 
40 
30 
30 
30 
30 
30 
30 


1 
3 

5 
1 

16 
17 
17 
18 
20 
23 
28 
43 
53 


Pulsations 
per  minute. 

270 

280 

300 

295 

280 

276 

260 

250 

255 
275 
260 
270 
260 
260 
270 
290 


REMARKS. 

Injected  intravenously  0.0017  gram  dialysis-venom-globulin 
from  the  dried  venom  of  the  Crolalus  adamanteus. 


Clot  formed  in  canula. 
Injected  0.0034  gram. 


Struggles. 


The  Actions  of  the  Venom  Globulins  on  Animals  with  Cut  Pneumoyastric 
Nerves. — In  five  experiments  on  animals  with  cut  pneumogastric  nerves — one  with 
the  water-venom-ylobulin,  two  with  copper-venom-ylobulin,  one  with  dialysis-venom- 
(jlolnilin  (all  from  the  Crotalns  adamanteits),  and  one  with  the  icater-venom-ylobulin 
of  the  Cobra — there  was  a  tendency  to  a  lowered  pulse-rate,  although  in  one 
experiment  there  was  a  primary  increase,  and  in  another  a  slight  increase  above 
the  healthy  number  after  repeated  injections.  The  effects  were  generally  less 
than  in  normal  animal. 


THE    ACTION    OF    VENOMS   UPON    THE    PULSE-KATE. 


75 


X<>.  46. 


Time  : 

Pulsations 

miu.   sec. 

pur  minute. 

Normal 

.    .    . 

205 

10 

220 

20 

280 

1     00 

210 

1     40 

190 

3     40 

no 

5     40 

180 

Experiment  No.  47. 

Time: 

Pulsations 

mill.    sec. 

per  minute. 

Normal 

.    .    . 

324 

0 

.    .     . 

15 

25 

812 

45 

318 

1     15 

264 

2     00 

300 

4     00 

304 

3     00 

276 

13     00 

288 

18     00 

310 

23     00 

319 

28 

Experiment  No.  48. 

Time: 

Pulsations 

min.    sec. 

per  minute. 

Normal 

.    .    . 

305 

20 

300 

40 

288 

1     10 

285 

3     10 

285 

5     10 

285 

7     10 

300 

9     10 

290 

23     10 

'310 

23     40 

310 

24     15 

310 

Experiment  No.  49. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    , 

300 

20 

300 

40 

300 

50 

300 

2     50 

300 

4     50 

300 

6     50 

300 

8     50 

300 

11     50 

300 

REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  0.0011 
gram  water -venom-olobulin  from  the  dried  veuom  of  the 
Crolalus  adamanteus. 


Clot  in  cauula. 


REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  water- 
venom-globulin  from  0.035  gram  dried  Cobra  venom  dis- 
solved in  1  c.  c.  distilled  water. 


Animal  broke  loose  from  canula. 


REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  0.0012 
gram  copper-venom-globulin  from  the  dried  venom  of  the 
Crotalus  adamanteus. 


Injected  0.0024  gram. 


Killed. 


REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  0.0012 
gram  copper-venom-globulin  from  the  dried  venom  of  the 
Crotalus  adamanteus. 


THE    VENOMS    OF    CERTAIN    TH A N A T 0 P H I D E 


Time  : 

Pulsations 

rain.   sec. 

per  minute. 

13      50 

300 

15     50 

300 

16      10 

300 

16     20 

300 

16     30 

300 

16     45 

300 

17     45 

300 

19     45 

300 

21     45 

300 

23     45 

270 

25     45 

270 

26     45 

270 

27     00 

270 

Experiment  No.  50. 

Time  : 

Pulsations 

mill.    sec. 

per  minute. 

Normal         .  .   . 

310 

10 

305 

20 

300 

30 

300 

50 

310 

1     50 

300 

4     20 

310 

6     20 

300 

8     20 

295 

10     20 

295 

12     20 

300 

17     50 

300 

18     20 

300 

18     40 

310 

19     00 

.    .    . 

19     15 

320 

19     20 

330 

21     50 

320 

23     00 

310 

25     00 

310 

27     00 

310 

29     00 

310 

34     00 

305 

34     30 

300 

38     30 

290 

41     00 

280 

47     00 

217 

49     00 

•    . 

REMARKS. 


Injected  0.0024  gram. 


Struggles. 


Animal  killed  by  pithing. 


REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  0.0017 
gram  dialysis- venom-globulin  from  the  dried  venom  of  the 
Crotalus  adamanteus. 

Struggles. 


Struggles. 

Injected  0.0034  gram. 

<t  «          « 

Struggles. 


Dead. 


The  Actions  of  Venom  Glolmlins  on  the  Pulse-rate  in  Animals  ivitli  the  Pneumo- 
gastric Nerves  and  Cervical  Spinal  Cord  Cut. — In  four  experiments  in  which  the 
pneumogastric  nerves  and  spinal  cord  in  the  middle  cervical  region  were  cut — one 
was  made  with  the  water-venom-globulin,  one  with  the  copper-vcnom-glolmlin,  and 
two  with  dialysis-venom-globulin  of  the  Crotalus  adamanteus:  in  one  experiment 


THE  ACTION  OF  VENOMS  UPON  THE  PULSE-RATE. 


77 


there  was  a  fall  followed  by  a  rise  to  the  normal,  and  succeeded  by  a  slight  fall ; 
in  a  second  the  pulse-rate  always  remained  below  normal,  while  in  the  third  there 
was  an  almost  inappreciable  rise,  this  followed  by  a  fall,  and  by  an  increase  due  to 
a  further  injection  of  the  poison.  The  last  showed  a  slight  fall,  then  a  return  to 
the  normal. 


Experiment  No.  51. 


Time  : 

Pulsations 

min.    stjc. 

per  minute. 

Normal 

250 

10 

250 

30 

215 

1     00 

240 

1     10 

240 

"2     10 

245 

3     10 

245 

5     10 

245 

7      10 

245 

9     10 

245 

11     10 

250 

15     10 

250 

17     40 

245 

19     00 

240 

21     00 

240 

23     00 

240 

25     00 

240 

27     00 

240 

Experiment  No.  52. 

Time  : 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    . 

255 

10 

255 

20 

240 

40 

250 

1     00 

250 

3     30 

240 

5     30 

225 

9     30 

225 

11     30 

210 

13     30 

210 

16     30 

210 

17     00 

204 

17     30 

210 

18     00 

210 

20     00 

210 

24     00 

195 

26     00 

180 

28     00 

180 

30     00 

180 

32     00 

180 

34     00 

187 

REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.0011  gram  watcr-venom-ylobulin  from  the  dried  venom 
of  the  Crotalus  adamanteus. 


Killed. 


REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
0.0048  gram  copper -venom- globulin  from  the  dried  venom 
of  the  Crotalus  adamanteus. 


Injected  0.0048  gram. 


Killed. 


78 


THE    VENOMS    OF    CERTAIN    THANATOPHIDE^E. 


Experiment  No.  53. 


Normal 


Time  : 

Pulsations 

min. 

sec. 

per  minute. 

.  . 

240 

10 

240 

30 

245 

1 

00 

230 

3 

00 

220 

6 

00 

220 

8 

30 

220 

10 

30 

230 

12 

30 

230 

12 

50 

220 

13 

10 

225 

13 

30 

210 

13 

50 

210 

15 

00 

200 

16 

00 

190 

REMARKS. 

Pneuinogastric  nerves  and  cord  cut.  Injected  intravenously 
0.0017  gram  dialysis-venom-globulin  from  the  dried  venom 
of  the  Crolalus  adamanleus. 


Injected  0.0034  gram. 


18     00 


Experiment  No.  54. 


Normal 


Time: 
min.   sec. 


10 

20 
30 
40 
50 
00 
10 
20 
00 


Pulsations 

per  minute. 

300 

290 
290 
300 
300 
300 
300 
300 
300 


Dead. 


REMARKS 

Pneumogastrie  nerves  and  cord  cut.  Injected  intravenously 
0.0068  gram  dialysis-venom-globulin  from  the  dried  venom 
of  the  Crotalus  adamanleus. 

Tremors. 


Clot  formed  in  canula. 
Dead. 


A  review  of  the  results  of  these  experiments  with  the  globulins  on  the  pulse-rate 
in  normal  animals  indicates  that  water-venom-globulin  is  the  most  potent,  and  the 
copper-venom-globulin  the  least  so.  With  the  former  there  occurred  in  four  of  the 
six  experiments  a  primary  increase  followed  by  a  fall,  while  in  the  other  two  there 
was  a  diminution  from  the  first.  In  experiments  with  the  copper-venom-globuliu 
and  dialysis-venom-globulin  there  was  always  a  primary  increase,  and  in  four  out  of 
the  five  experiments  this  was  followed  by  a  decline. 

After  section  of  the  pneumogastric  nerves  a  primary  increase  (due  probably  to 
some  accidental  cause)  occurred  in  one  out  of  the  five  experiments,  in  two  of 
the  other  four  there  at  first  was  no  appreciable  change,  and  then  a  diminu- 
tion, while  in  the  remaining  two  there  was  a  lessening  of  the  rate  from  the 
time  of  injection.  These  results  suggest  that  the  increase  of  the  pulse-rate,  which 
occurred  in  animals  with  intact  vagi,  was  in  some  degree  at  least  dependent  upon 
an  influence  exerted  through  the  pneumogastric  centres  and  nerves.  It  will  be 
observed  that  we  here  have  results  which  are  directly  opposed  to  what  we  have 
seen  with  pure  venom ;  that  is  a  lessened  tendency  to  the  primary  increase  of  the 


THE    ACTION    OF    VENOMS   UPON    THE    I>  U  L  SE-R  A  T  E.  79 

pulse  after  section  of  the  pneumogastric  nerves.  If  the  increase  in  the  pulse-rate 
in  normal  animals  is  due  for  the  most  part  to  excitation  of  the  accelerator  centres, 
whereby  impulses  are  generated  which  pass  chiefly  through  the  accelerator  fibres 
running  in  the  spinal  cord,  it  would  seem  probable  that  the  accelerator  impulses 
induced  by  the  globulins  take  for  the  most  part  the  course  of  the  fibres  through 
the  pneumogastric  nerves,  but  are  much  feebler  than  the  impulses  which  are  gene- 
rated by  the  pure  venoms,  and  which  take  their  path  chiefly  through  the  fibres  in 
the  spinal  cord. 

After  section  of  both  the  pneumogastric  nerves  and  cervical  spinal  cord,  we 
found  in  all  of  our  experiments  a  diminution  in  the  heart-beats ;  this  must  be  due 
to  a  direct  action  qf  the  globulin  upon  the  heart. 

It  therefore  seems  probable  that  the  globulins  cause  a  primary  increase  of  the 
pulse  by  an  excitation  of  the  accelerator  centres,  whereby  impulses  are  conveyed 
principally  by  the  accelerator  fibres  passing  through  the  pneumogastric  nerves; 
and  a  diminution  of  the  heart  beats  by  a  direct  action  on  the  heart. 


SECTION  III. — THE  ACTIONS  OF  VENOM  PEPTONES  UPON  THE  PULSE-RATE 

TJw  Action  of  Venom  Peptones  on  the  Pulse-rate. — In  seven  experiments  made 
with  peptone  on  normal  animals — four  with  the  peptone  from  the  venom  of  the 
Crotalus  adamanteus  ;  one  with  that  of  the  Anciatrodon  piscivorus  ;  and  two  with 
that  of  the  Cobra — we  find  results  which  vary  and  which  resemble  closely  those 
obtained  by  the  administration  of  pure  venom.  In  three  experiments  there  was  a 
primary  increase  of  pulse  followed  generally  by  a  diminution ;  in  three  the  pulse 
remained  below  normal ;  while  with  Ancistrodon  peptone  there  was  a  primary  fall 
of  rate  followed  by  a  rise. 

The  differences  in  the  results,  as  in  previous  experiments,  do  not  seem  to 
depend  at  all  upon  the  dose  or  the  variety  of  venom  from  which  the  peptone  was 
obtained. 

Experiment  No.  55. 

Timi- :  Pulsations  REMARKS 

min.    tec.        per  minute. 

Normal          .   .   .  280        Injected   intravenously  the  peptone  from  0.015  gram  dried 

20  102  venom  of  the  Crotalus  adamanteus. 

30  190 

40  190 

50  190 

1     00  180 

3     00  190 

6     00  340         Struggles. 

11     00  285         Struggles.     Broke  loose. 
49     00  Dead. 


80 


THE    VENOMS   OF    CERTAIN    Til  A  N  A  T  OP  HID  E  M. 


Experiment  No.  56. 


Time  : 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    . 

225 

10 

260 

30 

260 

1     00 

285 

2     00 

270 

5     00 

260 

9     00 

250 

Experiment  No.  57. 

Time: 

Pulsations 

min.  sec. 

per  minute. 

Normal 

.    .    . 

280 

30 

280 

1     00 

270 

1     30 

285 

4     30 

270 

10     30 

270 

10     50 

270 

11     10 

270 

11     30 

270 

Experiment  No.  58. 

Time: 

Pulsations 

min.  sec. 

per  minute. 

Normal 

.    .    . 

270 

10 

210 

20 

270 

30 

270 

1     00 

280 

1     30 

290 

2     00 

290 

2     30 

290 

3     00 

260 

5     00 

2GO 

5     20 

260 

5     40 

260 

6     00 

260 

6     30 

255 

1     00 

250 

7     30 

240 

8     00 

260 

Experiment  No.  59. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    . 

300 

10 

175 

30 

110 

1     00 

285 

1     20 

290 

1     40 

300 

2     00 

310 

REMARKS. 

Injected    intravenously  the  peptone  from   0.03  gram   dried 
venom  of  thu  Crotalus  adamanteus. 


Killed  by  pithing. 


REMARKS. 

Injected   intravenously  the  peptone  from  0.015  gram  dried 
venom  of  the  Crotalus  adamanleus. 


Injected  double  the  amount. 


REMARKS. 

Injected  intravenously  the  peptone  from  0.015  gram  dried 
venom  of  the  Crotalus  adamanleus. 


Injected  a  similar  quantity. 


Injected  double  the  quantity. 


REMARKS. 


Injected   intravenously  the   peptone  from  0.05   gram  dried 
venom  of  the  Ancistrodon  piscivorus. 


THE  ACTION  OF  VENOMS  UPON  THE  PULSE-RATE. 


81 


Time  : 

Pulsations 

niin.   sec. 

per  minute. 

2     20 

340 

2     40 

315 

5     40 

340 

5     50 

348 

6     00 

340 

6     20 

340 

6     30 

340 

13     30 

Experiment  No.  60. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal          .   .  . 

225 

10 

220 

20 

220 

30 

220 

40 

230 

1     00 

230 

1     20 

220 

3     20 

204 

fi     20 

165 

11     20 

280 

16     20 

260 

16     50 

200 

17     50 

150 

18     20 

100 

18     50 

... 

19     00 

130 

19     10 

190 

19     30 

110 

19     50 

38 

20     10 

35 

20     30 

35 

Experiment  No.  61. 

Time: 

Pulsations 

mill.   sec. 

per  minute. 

Normal          .  .   . 

290 

10 

300 

15 

310 

30 

240 

50 

245 

3     20 

225 

8     20 

97 

10     20 

72 

10     40 

300 

10     50 

300 

11     20 

105 

11     40 

85 

12     00 

120 

"12     20 

90 

12     40 

11       May,  1886. 

REMARKS. 


Injected  peptone  from  0.01  gram  venom. 


Killed. 


REMARKS. 

Injected  intravenously  the  peptone  from  0.005  gram  dried 
Cobra  venom. 


Struggles. 
Convulsive  twitchings. 

Blood  is  asphyxiated  ;  no  respiration. 


Killed. 


REMARKS. 

Injected  intravenously  the  peptone  from  0.06   gram   dried 
Cobra  venom. 


Tonic  convulsions. 

Convulsive   twitchings ;    asphyxiated    blood ;    respiration 
ceased. 


Dead. 


82 


THE  VENOMS  OF  CERTAIN  THANATOPHIDE.E. 


The  Actions  of  Venom  Peptones  on  Animals  in  which  the  Pneumogastric  Nerves 
had  been  Oat. — Four  experiments  were  made  with  the  peptone  on  animals  the 
pneumogastric  nerves  of  which  had  been  previously  cut.  In  three  of  the  four  there 
was  a  primary  increase  in  the  pulse,  while  in  the  fourth  there  was  a  temporary 
diminution  followed  by  a  rise  above  normal.  These  experiments  are  in  accord  with 
those  made  with  pure  venom,  and  indicate  a  greater  tendency  to  primary  pulse 
frequency  after  section  of  the  pneumogastric  nerves. 

One  of  the  above  experiments  was  made  with  the  peptone  from  the  Crotalus 
adamanteus ;  one  with  the  Ancistrodon  piscivorus ;  and  two  with  the  Cobra. 


REMARKS. 

Pneumogastric  nerves  cut.    Injected  intravenously  the  peptone 
from  0.015  gram  dried  venom  of  the  Crolalus  adamanteus. 

Struggles. 


Experiment  No.  62. 

Time: 

Pulsations 

inin. 

sec. 

per  minute. 

Normal 

,    . 

285 

10 

285 

30' 

285 

40 

300 

50 

300 

1 

00 

300 

1 

20 

300 

1 

30 

300 

3 

30 

315 

8 

30 

330 

15 

30 

345 

20 

30 

325 

25 

30 

315 

30 

30 

315 

35 

00 

315 

40 

00 

315 

45 

00 

270 

50 

00 

255 

62 

00 

285 

Struggles. 


Experiment  No.  63. 


Time: 


Pulsations 


Normal 


min.   sec.        per  minute. 


30 

40 
50 
00 
20 
40 
00 
30 
2  40 

2  50 

3  00 

4  20 


295 
315 
315 
310 
310 
315 
320 
330 
310 
102 
150 
240 


Killed. 


REMARKS. 

Pneumogastric  nerves  cut.  Injected  intravenously  the  peptone, 
from  0.015  gram  dried  venom  of  the  Ancistrodon  pisci- 
vorus. 


Dead. 


THE    ACTION   OF    VENOMS    U  P  0  N    THE    PULSE-RATE. 


83 


Experiment  No.  64. 

Time:  Pulsations 

min.   sec.        per  minute. 


REMARKS. 


Normal          .  .  . 
10 
20 

230 
235 
240 

Pneumogastric  nerves  cut.    Injected  intravenously  the  peptone 
from  0.005  gram  dried  Cobra  venom. 

40 

230 

1     00 

230 

1     30 

230 

3     30 

230 

5     30 

230 

1     30 

230 

9     30 

220 

10     00 

220 

21     30 
25     30 

225 

230 

Switchings. 

20     30 

235 

Killed. 

Experiment  No.  65. 

Time: 

Pulsations 

REMARKS. 

niiu.   sec. 

Normal          .   .   . 
10 
20 

per  minute. 

265 
265 
255 

Pneumogastric  nerves  cut.    Injected  intravenously  the  peptone 
from  0.006  gram  dried  Cobra  venom. 

40 

260 

1     00 

260 

3     00 

270 

5     00 

270 

16     00 

275 

34     00 

•    • 

Dead. 

The  Actions  of  Venom  Peptones  upon  the  Pulse-rate  of  Animals  after  Section 
of  the  Pneumorjastric  Nerves  and  Cervical  Spinal  Cord. — Six  experiments  made 
on  animals  in  which  the  heart  was  cut  off  from  central  nervous  influence  by  section 
of  the  pneumogastric  nerves  and  section  of  the  spinal  cord  in  the  middle  cervical 
region  gave  uniform  results.  Three  were  made  with  peptone  from  the  venom 
of  the  Crotalus  adamantew;  two  with  the  peptone  from  the  Ancistrodon  piscivorua, 
and  one  with  that  of  the  Cobra.  In  all  of  these  experiments  there  was  a  diminu- 
tion of  the  pulse-rate,  and  usually  this  was  well  marked.  These  results  are  also 
in  accord  with  what  was  found  in  experiments  with  pure  venom. 


Experiment  No.  66. 


Normal 


Time: 

Pulsations 

min. 

sec. 

per  minute. 

. 

200 

10 

185 

20 

195 

40 

195 

1 

00 

190 

3 

00 

160 

13 

00 

195 

15 

00 

200 

REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
the  peptone  from  0.015  gram  dried  venom  of  the  Crotalus 
adamanteus. 


THE  VENOMS  OF  CERTAIN  T  II  A  N  A  T  0  PHI  D  E  M. 


Time  : 

Pulsations 

min.    sec. 

per  minute. 

17     00 

190 

17     30 

.    .    . 

19     30 

187 

21     30 

190 

23     30 

180 

25     30 

170 

31     30 

165 

34     30 

Experiment  No.  67. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    . 

282 

0 

.    .    . 

15 

276 

20 

.    .    . 

30 

264 

1     00 

264 

1     30 

246 

2     00 

234 

Experiment  No.  68. 

Time: 

Pulsations 

min.   sec. 

per  minute. 

Normal 

.    .    . 

324 

0 

.    .    . 

11 

300 

40 

318 

1     40 

276 

5     40 

272 

10     40 

276 

15     40 

306 

16     00 

•    •    • 

Ifi     06 

16     15 

306    . 

16     25 

300 

17     00 

276 

18     00 

270 

•    REMARKS 


23      00 


Injected  peptone  from  0.03  gram  dried  venom. 


Dead. 


REMARKS. 

Pneumogastric  nerves  and  cord  cut.  Injected  intravenously 
the  peptone  from  0.015  gram  dried  venom  of  the  Crotalus 
adamanteus. 


REMARKS. 

Pneumogastric  nerves  and  cord  cut.     Injected  intravenously 
the  peptone  from  0.015  gram  dried  Cobra  venom. 


j-  Injected  a  similar  dose. 


Dead. 


In  the  above  series  of  experiments  with  venom  peptones  we  find  results  which 
agree  with  those  in  which  the  pure  venoms  were  used.  We  conclude,  therefore, 
that  the  peptones  cause  a  primary  increase  and  a  secondary  diminution  of  the 
pulse-rate,  and  that  they  occasion  primary  hastening  of  the  heart  beat  by  excita- 
tion of  the  accelerator  centres  in  the  medulla,  and  that  the  impulses  are  carried 
through  fibres  passing  chiefly  by  the  spinal  cord.  This  increase  is  more  marked 
after  section  of  the  pneumogastric  nerves,  thus  suggesting  that  this  principle  has 
some  direct  or  indirect  effect  upon  the  pneumogastric  centres,  tending  to  slow  the 
action  of  the  heart  and  to  neutralize  the  accelerator  influence.  Peptones  cause 
the  diminution  of  the  heart  beat  by  a  direct  action  on  that  organ. 


THE    ACTION    OF    VENOMS    UPON    ARTERIAL    PRESSURE.        85 


CHAPTER    VIII. 

THE  ACTION  OF  VENOMS  AND  THEIR  ISOLATED  GLOBULINS  AND 
PEPTONES  UPON  THE  ARTERIAL  PRESSURE. 

SECTION  I. — PURE  VENOM. 

THE  experiments  made  on  the  blood  pressure  with  venoms  and  their  isolated 
poisons  were  all  made  on  rabbits.  The  manometer  tube  was  connected  with  one 
of  the  carotid  arteries,  and  the  injections  were  always  made  into  the  external 
jugular  vein  unless  otherwise  noted. 

Eighteen  experiments  were  performed  with  the  venoms  of  different  species  of 
serpents,  and  in  all  of  them  there  was  a  distinct  lowering  of  the  blood-pressure. 
It  fell  immediately  after  the  injection,  and  indeed  sometimes  before  injection  was 
complete,  and  the  fall  was  generally  so  marked  as  to  indicate  a  most  profound  action 
of  the  poison  upon  some  part  or  parts  of  the  circulatory  apparatus.  If  the  dose  be 
not  immediately  fatal  the  pressure  gradually  rises,  but  finally  undergoes  a  more  or 
less  steady  decline  to  death.  At  other  times  the  pressure  sinks  without  subsequent 
rise  until  death  ensues. 

The  tendency  in  Cobra  poisoning  is  to  a  decided  rise  of  pressure  following  the 
primary  fall.  In  five  out  of  six  experiments  with  this  venom  the  primary  fall  was 
followed  by  a  rise  which  went  above  the  normal. 

Of  the  eighteen  experiments,  five  were  made  with  the  venom  of  Crotalus  ada- 
manteus,  in  two  of  which  the  poison  was  given  hypodermatically;  two  with  that  of 
the  Crotalus  horridus  ;  two  with  the  venom  of  Ancistrodon  piscivorus  ;  one  each  with 
the  poisons  Ancistrodon  contortrix,  Crotalophorus  miliarius,  and  Daboia  Russell ii ; 
and  six  with  the  venom  of  the  Cobra.  In  all  cases  ether  was  given  freely  to  the 
animal  poisoned. 

Action  of  the  Pure  Venoms  upon  the  Arterial  Pressure  in  Normal  Animals. 


Experiment 

No.  1 

Time: 

min.   sec. 

Normal 

.    .    . 

20 

40 

1     00 

1     20 

1     40 

2     00 

5     00 

Pressure 
m.  m. 

126 
126 
126 
124 
122 
120 
118 
114 


REMARKS. 

Injected  into  the  thigh  of  a  large  rabbit  1  drop  of  fresh  venom 
from  the  Crotalus  adamanteus. 


Clot  formed  in  canula. 


86 


THE    VENOMS   OF    CERTAIN    T  II  A  N  A  T  0  P  H  I  D  E 


Time: 

Pressure 

min.   sec. 

in.  m. 

7     00 

84 

8     00 

84 

9     00 

84 

10     00 

82 

11     00 

82 

12     00 

78 

13     00 

82 

20     00 

52 

21     30 

56 

23     00 

64 

25     00 

56 

26 

Experiment  No.  2. 

Time  : 

Pressure 

min.  sec. 

m.  m. 

Normal          .   .  . 

144 

20 

144 

40 

138 

1     00 

136 

1     20 

130 

1     40 

130 

2     00 

126 

Experiment  No.  3. 

Time: 

Pressure 

min.   sec. 

m.  m. 

Normal          .  .   . 

70 

10 

58 

20 

54 

30" 

60 

40 

68 

50 

68 

1     00 

68 

1     20 

68 

1     40 

62 

2     00 

58 

2     20 

54 

2     40 

44 

Experiment  No.  4. 

Time  : 

Pressure 

min.  sec. 

m.  m. 

Normal          .  .   . 

MO 

5 

76 

10 

72 

20 

64 

30 

62 

40 

60 

1     00 

58 

1     20 

58 

1     40 

56 

2     10 

54 

REMARKS. 


Struggles  followed  by  death. 


REMARKS. 

Injected  into  the  thigh  of  a  rabbit  3  drops  of  fresh  venom 
from  the  Crolalus  adamanteus. 


Struggles.     Animal  tore  loose  from  the  canula. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cro- 
talus  adamanleus  in  1  c.  c.  distilled  water. 


Death. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cro- 
talus  adamanteus  dissolved  in  1  c.  c.  distilled  water. 


THE    ACTION    OF    VENOMS    UPON    ARTERIAL    PRESSURE.        87 


Time  : 

Pressure 

inin.   sec. 

m.  ra. 

4     00 

45 

7     00 

40 

8     00 

110 

8     10 

94 

8     20 

74 

8     30 

78 

8     40 

76 

8     50 

60 

10     30 

56 

13     00 

64 

13     30 

13     50 

50 

14     00 

50 

10     00 

.  .  . 

16     05 

48 

16     30 

44 

n   oo 

Experiment  No.  5. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal 

.    .    . 

124 

10 

100 

20 

60 

30 

96 

40 

84 

1     00 

70 

1     20 

56 

1     40 

48 

1     55 

44 

4     00 

38 

7     00 

32 

8     00 

Experiment  No.  6. 

Time: 

Pressure 

min.    sec. 

m.  m. 

Normal 

.    .    . 

104 

5 

84 

10 

68 

20 

74 

30 

80 

40 

78 

50 

70 

1     00 

64 

1     10 

60 

1      20 

56 

1     30 

52 

1     40 

48 

3     40 

40 

5     40 

44 

7     40 

46 

9     40 

42 

10     10 

38 

REMARKS. 


Struggles. 


Injection  as  before. 


Dead.     Heart  in  complete  diastole.     Ecchymoses  in  pericar- 
dium and  peritoneum.     Blood  incoagulable. 

REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 

talus  adamanleus  dissolved  in  1  c.  c.  distilled  water. 
Struggles. 


Pulse  feeble. 
Dead. 


REMARKS. 


Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 
talus  horridus  dissolved  in  1  c.  c.  distilled  water 


Convulsions. 

Dead.     Some  ecchymoses ;  blood  fluid. 


88 


THE    VENOMS    OF    CERTAIN    T  11  A  N  A  T  O  P  H  1 1)  E 


Experiment 

No.  7. 

Time  : 

Pressure 

inin.   sec. 

m.  m. 

Normal 

.    .    . 

110 

5 

76 

10 

76 

20 

78 

30 

70 

2     40 

60 

3     00 

44 

5     00 

42 

6     30 

40 

1     30 

36 

8     00 

32 

8     30 

26 

9     00 

20 

10     00 

10 

Experiment 

No.  8. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

138 

20 

•  80 

30 

64 

40 

74 

1     00 

84 

1     30 

76 

1     50 

60 

2     10 

74 

2     30 

74 

3     00 

84 

4     00 

Experiment 

No.  9. 

Time: 

Pressure 

min.   sec. 

m.  m. 

Normal 

... 

134 

10 

108 

20 

72 

30 

70 

7     00 

70 

1     30 

72 

2     00 

74 

2     30 

70 

* 

3     00 

70 

5     00 

70 

5     30 

68 

5     35 

76 

5     45 

70 

6     05 

60 

6.    15 

62 

6     25 

66 

6     45 

60 

7     05 

52 

REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 
talus  horridus  dissolved  in  1  c.  c.  distilled  water. 


Animal  broke  loose  from  mouth-piece,  and  was  firmly  held 
and  refixed. 


Dead.     Respiration  failed  before  the  heart. 


REMARKS. 

Injected  intravenously  0.004  gram  dried  venom  of  the  Ancis- 

Irodon  piscivorus  dissolved  in  1  c.  c.  distilled  water. 
Convulsions. 


Injected  as  above. 
Struggles. 


Killed  by  pithing. 


REMARKS. 


Injected  intravenously  0.004  gram  dried  venom  of  the  Ancia- 
trodon  piscivorus  dissolved  in  0.5  c.  c.  distilled  water. 


Injection  repeated  as  before 


Convulsive  movements. 


THE    ACTION    OF    VENOMS    UPON   ARTERIAL    PRESSURE.        89 


Time  : 

Pressure 

min.   sec. 

m.  m. 

7      15 

54 

7     25 

72 

7     35 

70 

7     45 

66 

7     55 

104 

8     05 

120 

8     15 

100 

8     25 

86 

Experiment 

No.  10. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal 

... 

96 

10 

70 

30 

76 

1     00 

72 

1     30 

72 

2     00 

72 

2     30 

70 

4     30 

48 

5     30 

48 

5     50 

42 

6     30 

50 

6     50 

50 

7     50 

46 

10     00 

Experiment 

No.  11. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal 

•    •    • 

170 

20 

122 

30 

120 

40 

136 

50 

116 

1     00 

150 

1      10 

84 

2     10 

108 

2     40 

106 

2     50 

80 

3     20 

84 

5     20 

70 

7     20 

74 

9     20 

80 

Experiment 

No.  12. 

Time: 

Pressure 

min.   sec. 

m.  m. 

Normal 

.    .    . 

130 

10 

110 

20 

102 

30 

96 

40 

88 

12       June,  1886. 

REMAKK3. 


Animal  died  in  a  few  minutes. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 
Irodon  contortrix  dissolved  in  1  c.  c.  distilled  water. 


Injection  repeated. 
Struggles. 


Injection  repeated. 
Dead.     Heart  flabby 


blood  incoagulable  ;  no  ecchymoses. 


REMARKS. 


Injected  intravenously  0.003  gram  dried  venom  of  the  Crota- 
lophorus  miliarius  dissolved  in  1  c.  c.  distilled  water. 


Injection  repeated  as  before. 


Killed  by  pithing. 


REMARKS. 


Injected  intravenously  0.003  gram  dried  Cobra  venom  dis- 
solved in  1  c.  c.  distilled  water. 


90 


THE    VENOMS    OF   CERTAIN   THANATOPHIDEJS. 


Time: 

Pressure 

min.   sec. 

m.  m. 

50 

70 

1     00 

78 

1     10 

70 

1     20 

52 

1     30 

52 

1     40 

50 

2     00 

38 

2     20 

34 

3     20 

Experiment  No.  13. 

Time: 

Pressure 

min.   sec. 

m.  m. 

Normal 

... 

140 

10 

150 

30 

140 

1     00 

134 

1     20 

134 

3     20 

140 

5     20 

148 

Experiment  No.  14. 

Time: 

Pressure 

min.   sec. 

m.  m. 

Normal 

... 

132 

1     00 

122 

3     00 

120 

8     00 

130 

10     00 

138 

15     00 

106 

17     00 

66 

18     00 

48 

19     00 

Experiment  No.  15. 

Time: 

Pressure 

min.   sec. 

m.  m. 

Normal 

.    .    . 

145 

20 

142 

40 

135 

1     00 

128 

1     30 

130 

2    00 

140 

4     00 

150 

9     00 

143 

12     00 

138 

14     00 

158 

20     00 

135 

REMARKS. 


Convulsions. 


Dead.     Heart  in  systole;  blood  clotted;  no  ecchymoses. 


REMARKS. 

Injected   intravenously  0.003  gram  dried  Cobra  venom  dis- 
solved in  1  c.  c.  distilled  water. 


Death  from  hemorrhage  ;  artery  torn. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  Cobra  venom  dis- 
solved in  1  c.  c.  distilled  water  with  a  few  crystals  of  sodic 
chloride. 


Dead 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cobra 
dissolved  in  1  c.  c.  distilled  water. 


Respiration  ceased ;  artificial  respiration  used. 


THE  ACTION  OF  VENOMS  UPON  ARTERIAL  PRESSURE.   91 


Experiment  No.  16. 


Time  : 

Pressure 

min.   sec. 

m.  ra. 

Normal 

.   .  . 

120 

20 

108 

30 

96 

40 

88 

1     00 

90 

1     20 

82 

1     40 

96 

4     40 

94 

7     40 

100 

8     40 

122 

9     10 

156 

15     00 

Experiment 

No.  17. 

Time  : 

Pressure 

mil),   sec. 

m.  m. 

Normal 

.    .    . 

90 

10 

94 

20 

66 

30 

84 

40 

90 

1     00 

88 

1     30 

86 

2     00 

78 

2     10 

74 

4     10 

90 

4     40 

96 

5     10 

92 

6     10 

72 

6     20 

60 

6     50 

32 

7     30 

24 

8     20 

6 

Experiment 

No.  18. 

Time: 

Pressure 

min.   sec. 

m.  m. 

Normal 

.    .    . 

110 

10 

112 

11 

.    .    . 

15 

80 

20 

64 

30 

46 

40 

30 

50 

54 

1     00 

46 

1     15 

46 

2     00 

s 

REMARKS. 

Injected  intravenously  0.005  gram  dried  Cobra  venom  dis- 
solved in  1  c.  c.  distilled  water  with  a  little  sodic  chloride 
and  filtered. 


A  clot  was  probably  beginning  to  form  in  the  canula,  and  no 

dependence  is  to  be  placed  upon  the  after  record. 
Struggles.     Clot  in  canula. 
Dead. 


REMARKS. 

Injected  intravenously  0.015  gram  dried  Cobra  venom  dis- 
solved in  1  c.  c.  distilled  water. 


Dead. 


REMARKS. 

Injected  intravenously  0.005  gram  dried  venom  of  the  Daboia 

Russellii  dissolved  in  0.5  c.  c.  distilled  water. 
Pressure  falling. 


Violent  general  convulsions. 


Dead.     Heart  in  diastole;  no  ecchymoses ;  after  twenty-four 

hours  the  blood  is  still  fluid. 
Artificial  respiration  was  used   in  this  experiment  from  the 

beginning. 


92 


THE    VENOMS    OF    CERTAIN    T  H  A  N  A  T  0  P  H  I  D  E  JE. 


This  single  experiment  confirms  the  statements  of  Fayrer  and  of  Wall  in  regard 
to  the  convulsivant  power  of  Daboia.  The  spasms  are  not  due  to  defect  of  oxygen, 
as  they  arise  early  and  occur  despite  the  use  of  artificial  respiration.  Ancistrodon 
venom  seems  to  have  the  same  capacity  to  produce  convulsions. 

77<e  Action  of  Pure  Venoms  on  the  Blood  Pressure  of  Animals  with  Cut  Pneumo- 
gastric  Nerves. — After  section  of  the  pneumogastric  nerves,  including  the  depressor 
fibres,  we  find  that  the  same  alterations  occur  in  the  blood  pressure  as  in  normal 
animals.  Nine  experiments  were  made  altogether:  two  with  the  venom  of  the 
Crotalus  adamanteus ;  one  with  the  Crotalus  liorridus  ;  two  with  the  Ancistrodon 
piscivorus  ;  one  with  the  Ancistrodon  contortrix ;  and  three  with  the  Cobra. 


Experiment  No.  19. 

Time  : 

inin. 

sec. 

Normal          .  . 

10 

30 

1 

00 

1 

30 

2 

00 

2 

30 

5 

30 

7 

00 

8 

30 

8 

40 

9 

00 

9 

10 

9 

20 

9 

30 

Experiment  No.  20. 


Normal' 


Time: 
min.   sec. 

10 
20 
30 
40 
50 

1  00 
1  10 
1  20 
1  30 


Pressure 
m.  m. 
96 
74 
G8 
68 
76 
64 
60 
44 
44 
48 
42 
46 
44 
44 
44 


Pressure 
m.  m. 
130 
100 

90 

96 

76 

56 

50 

38 

32 

22 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  "CVo- 
talus  adamanleus  dissolved  in  1  c.  c.  distilled  water. 


Injected  the  same  as  above. 


Dead. 


REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 
lalus  adamanleus  dissolved  in  1  c.  c.  distilled  water. 


Dead. 


THE  ACTION  OF  VENOMS  UPON  ARTERIAL  PRESSURE.   93 


Experiment  No.  21. 

Time :  Pressure 

miu.   sec.  in.  in. 


Normal 


144 


REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 
lalus  horridus  dissolved  in  1  c.  c.  distilled  water. 


10 

146 

Struggles. 

20 

124 

Violent  struggles. 

40 

124 

1     00 

94 

1     20 

80 

1     40 

70 

2     00 

56 

2     20 

54 

4     20 

54 

5     50 

44 

• 

8     00 

12 

Dead. 

Experiment  No.  22. 

Time: 

Pressure 

REMARKS. 

miii.   sec. 

m.  m. 

Normal          .   .  . 

90 

Injected  intravenously  0.0035  gram  dried  venom  of  the  Ancis- 

8 

76 

trodon  piscimrus  dissolved  in  1  c.  c.  distilled  water. 

10 

54 

20 

44 

30 

50 

Convulsions. 

40 

54 

1     00 

44 

1     20 

24 

1     40 

Dead. 

Experiment  No.  23. 

• 

Time: 

Pressure 

REMARKS. 

min.   sec. 

m.  m. 

Normal          .  .   . 

110 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 

10 

84 

trodon  piscivorus  dissolved  in  1  c.  c.  distilled  water. 

20 

64 

• 

30 

68 

Struggles. 

40 

78 

50 

76 

1     00 

72 

1     20 

66 

3     50 

52 

5     50 

64 

Struggles. 

6     00 

86 

Convulsions. 

8     00 

100 

10     00 

74 

12     00 

70 

14     00 

66 

19     00 

70 

Injection  repeated,  using  the  same  amount. 

19     10 

70 

19     20 

52 

19     30 

98 

19     40 

68 

19     50 

90 

94 


THE  VENOMS  OF  CERTAIN  T  H  AN  A  T  0  P  H  I  DE 


Time  : 

Pressure 

min.  see. 

in.  in. 

20  00 

90 

20  20 

72 

21  20 

60 

23  20 

56 

25  20 

60 

28  20 

70 

33  20 

70 

38  20 

66 

44  20 

58 

44  30 

50 

44  40 

48 

44  50 

44  ' 

45  00 

36 

45  10 

26 

Experiment  No.  24. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal    .  .  . 

154 

10 

114 

20 

86 

30 

76 

40 

82 

1  00 

84 

1  50 

80 

4  20 

98 

1  00 

100 

7  05 

138 

7  10 

110 

7  20 

106 

7  40 

108 

8  00 

98 

8  30 

88 

9  00 

80 

11  30 

78 

11  40 

76 

12  00 

70 

12  30 

66 

13  00 

68 

13  30 

68 

19  00  - 

72 

19  20 

54 

19  40 

50 

20  20 

44 

21  50 

40 

22  50 

38 

REMARKS. 


Third  injection,  same  amount. 


Dead. 


REMARKS 


Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 
trodon  contortrix  dissolved  in  1  c.  c.  distilled  water. 


Injection  repeated. 
Struggles. 


Third  injection. 


Fourth  injection. 


Dead.     Heart  in  diastole ;  blood  remains  fluid ;  muscles  all 
respond  to  electrical  irritation ;  motor  nerves  react  feebly. 


THE    ACTION    OF    VENOMS    UPON    A  K  T  E  ill  A  L    PRESSURE.        95 


Experiment  No.  25. 


Time  : 


Normal 


Mill. 

sec. 

111.  III. 

148 

10 

146 

30 

186 

1 

00 

140 

1 

30 

140 

3 

30 

150 

6 

30 

150 

10 

30 

146 

14 

30 

152 

16 

30 

156 

Experiment  No.  26. 


Normal 


Time  : 

Pressure 

min 

.   sec. 

m.  m. 

. 

.    . 

134 

10 

136 

30 

126 

1 

00 

118 

1 

30 

118 

3 

30 

132 

5 

30 

136 

7 

30 

136 

9 

30 

136 

11 

30 

136 

18 

30 

188 

Experiment  No.  27. 


Normal 


Time: 
min.  sec. 

0 
10 
20 

1  00 

2  00 
4     00 

10 
15 


REMARKS. 

Injected  intravenously  0.003  gram  dried  Cobra  venom  dis- 
solved in  1  c.  c.  distilled  water  with  a  few  crystals  of  sodic 
chloride  and  filtered. 


Clot  formed  in  canula.     Animal  killed. 


REMARKS. 

Injected  intravenously  O.OOC  gram  dried  Cobra  venom  pre- 
pared as  in  the  foregoing  experiment. 


Convulsive  movements;  asphyxia;  respiration  ceased  in  three 
minutes. 


Pressure  REMARKS, 

m.  m. 

130         Injected  intravenously  0.003  gram  dried  Cobra  venom  dis- 
.  .  .  solved  in  1  c.  c.  distilled  water. 

130 
118 
118 
115 
.  .  .  Clot  in  canula. 

Dead  from  asphyxia 


The  Action  of  Pure  Venoms  on  the  Blood  Pressure  of  Animals  in  which  the 
Cervical  Spinal  Cord  had  been  Divided. — Upon  section  of  the  spinal  cord  in  the 
upper  cervical  region,  by  which  the  influence  of  the  vaso-motor  centres  in  the 
medulla  is  practically  destroyed,  the  primary  fall  of  pressure  from  venom  is  gener- 
ally very  slight,  and  after  this  diminution  there  is  a  secondary  rise  which  may  go 
above  the  normal.  In  one  experiment  with  Crotalus  adamanteus  venom  there 
was  a  rise  of  pressure  for  a  moment  at  the  time  of  injection ;  in  one  experiment 
with  Crotalus  horridus,  in  which  a  somewhat  larger  dose  was  used  than  in  the 
others,  there  was  a  distinct  rise  of  pressure  a  few  seconds  after  injection,  followed 
by  a  fall ;  and  in  the  experiment  with  the  Cobra  the  pressure  never  went  below 


96 


THE    VENOMS    OF    CERTAIN    THANATOPHIDEJ5. 


the  normal,  but  in  a  few  moments  a  rise  occurred  which  continued  to  increase  for 
half  an  hour,  when  the  animal  was  killed. 

In  this  series  we  observed  a  marked  difference  from  the  preceding  (unless  the 
dose  had  been  immediately  toxic),  since  the  profound  primary  fall  of  pressure  was 
not  observed,  excepting  in  a  very  slight  degree  if  at  all;  we  found,  however,  that 
the  ultimate  fall  of  pressure  still  occurred,  save  in  the  case  of  the  Cobra. 

Eight  experiments  were  made:  two  with  Crotalus  adamanteus ;  one  with  Cro- 
talus  horridus  ;  three  with  Ancistrodon  piscivorus  ;  one  with  Ancistrodon  contort  ri-x, 
and  one  with  Cobra  venom. 


Experiment  No.  28. 


Normal 


Time: 

Pressure 

uiin 

.  §ec. 

m.  m. 

. 

.    . 

62 

9 

70 

20 

56 

30 

56 

40 

58 

1 

00 

58 

1 

20 

56 

1 

"30 

48 

1 

40 

46 

2 

00 

44 

2 

20 

40 

2 

40 

38 

5 

20 

36 

6 

50 

36 

7 

20 

36 

8 

00 

•    •    • 

Experiment  No.  29. 


Normal 


Time : 
min.    sec. 


5 
10 
20 
30 
40 
50 
00 
30 
30 


3     30 


30 
30 
00 


Pressure 
m.  m. 
66 
60 
58 
58 
64 
62 
58 
56 
48 
40 
60 
56 
40 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cro- 
talus  adamanteus  dissolved  in  1  c.  c.  distilled  water. 


Dead. 


REMARKS. 

Injected  intravenously  0.006  gram  dried  venom  of  the  Cro- 
talus adamanteus  dissolved  in  1  c.  c.  distilled  water. 


Dead. 


THE    ACTION   OF   VENOMS   UPON  ARTERIAL   PRESSURE.       97 


Experiment  No.  30. 

Time  : 

Pressure 

REMARKS. 

min.  sec. 

m.  m. 

Normal          .   .   . 

30 

Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 

20 

30 

talus  horridus  dissolved  in  1  c.  c.  distilled  water. 

40 

46 

±     00 

42 

1     20 

38 

3     20 

26 

5     20 

26 

7     20 

26 

9     20 

24 

10     50 

30 

12     50 

30 

14     50 

28 

16     50 

26 

17     05 

26 

17     35 

10 

Conjunctival  reflexes  gone. 

18     00 

Dead. 

Experiment  No.  31. 

Time: 

Pressure 

REMARKS. 

min.  sec. 

m.  m. 

Normal          .  .   . 

56 

Injected  intravenously  0.007  gram  dried  venom  of  the  Ancis- 

10 

50 

trodon  piscivorus  dissolved  in  1  e.  c.  distilled  water. 

20 

46- 

30 

46 

40 

40 

50 

34 

1     00 

30 

3     00 

22 

5     00 

28 

7     00 

26 

10     00 

18 

Dead.     The  cord  proved  not  to  have  been  completely  cut  —  a 

few  fibres  of  the  posterior  columns  remaining  undivided. 

Experiment  No.  32. 

Time: 

Pressure 

REMARKS. 

min.   sec. 

m.  m. 

Normal          .  .   . 

58 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 

10 

54 

trodon  pianvorus  dissolved  in  1  c.  c.  distilled  water. 

20 

40 

30 

32 

Convulsions. 

40 

26 

50 

16 

Dead. 

Experiment  No.  33. 

Time: 

Pressure 

REMARKS. 

min.  sec. 

m.  m. 

Normal          .   .   . 

46 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 

10 

38 

trodon  piscivorus  dissolved  in  1  c.  c.  distilled  water. 

20 

40 

30 

38 

40 

40 

56 

48 

3     00 

38 

5     00 

30 

8     00 

28 

Dead. 

13       June,  1886. 


98 


THE   VENOMS   OF    CERTAIN    THANATOPHIDEJB. 


Experiment  No.  34. 

Time  : 

Pressure 

min.  sec. 

m.  m. 

Normal 

... 

52 

10 

44 

20 

46 

40 

50 

1  00 

54 

3  00 

46 

5  00 

36 

1  00 

34 

9  00 

34 

11  00 

30. 

13  00 

30 

15  00 

30 

17  00 

30 

19  00 

30 

21  00 

30 

23  00 

30 

25  00 

32 

27  00 

32 

29  00 

34 

56  00 

34 

61  00 

32 

75  00 

30 

Experiment  No.  35. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

... 

42 

10 

46 

30 

44 

1  00 

42 

3  00 

46 

6  00 

48 

9  00 

46 

12  00 

50 

15  30 

50 

18  30 

52 

21  30 

54 

24  30 

56 

27  30 

54 

27  40 

56 

28  00 

64 

28  30 

68 

30  30 

78 

REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 
trodon  contortrix  dissolved  in  1  c.  c.  distilled  water. 


Killed  by  pithing. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cobra 
dissolved  in  1  c.  c.  distilled  water  with  a  few  crystals  of 
sodic  chloride  and  filtered. 


Injected  the  same  as  the  foregoing. 


Clot  formed  in  canula.     Killed  animal  by  pithing. 


The  Action  of  Pure  Venoms  on  tJie  Blood  Pressure  of  Animals  in  wJiich  the 
Pneumogastric,  Depressor,  and  Sympathetic  Nerves  and  Spinal  Cord  have  been 
Severed. — Since  we  found  in  the  last  series  of  experiments  that  after  section  of  the 
cord  there  did  not  occur  such  a  decided  primary  fall  of  pressure,  it  seemed  obvious 
that  the  fall  of  pressure  must  be  due,  in  major  part  at  least,  to  a  toxic  depression 


THE  ACTION  OF  VENOMS  UPON  ARTERIAL  PRESSUKK 


99 


of  the  vaso-motor  centres  A  fall  of  pressure  does,  however,  ultimately  occur, 
and,  excepting  in  the  case  of  the  Cobra,  increases  until  death  ensues 

In  seven  other  experiments,  supplementary  to  the  above,  in  which  we  made 
section  of  the  pneumogastric,  depressor,  and  sympathetic  nerves  in  the  neck,  and 
section  of  the  spinal  cord  in  the  middle  or  upper  cervical  region,  thus  cutting  off 
both  the  heart  and  capillaries  from  centric  nervous  influence,  we  obtained  results 
which  were  practically  the  same 

Three  of  these  experiments  were  made  with  the  venom  of  the  Crotalus  adaman- 
ieus ,  one  with  that  of  the  Crotahw  liorridus ;  one  with  the  Ancistrodon  piecivorus; 
one  with  the  Ancistrodon  contortnx,  and  one  with  the  Cobra. 


Experiment  No  36 


Normal 


Time 
min    sec. 


10 

20 
30 
40 
00 
20 
40 
00 


2     20 


Experiment  No.  37. 


Normal 


Experiment  No  38. 


Normal 


Time: 
min.   sec. 

5 

10 
20 
30 
40 
50 


Pressure 

in.  in. 

62 
56 
46 
56 
52 
4G 
40 
36 
30 
24 


Time  : 

Pressure 

min. 

sec. 

m   m. 

48 

10 

46 

20 

48 

30 

46 

1 

00 

48 

1 

20 

46 

3 

20 

40 

3 

50 

32 

5 

50 

36 

7 

50 

30 

Pressure 
m.  m. 
30 
32 
28 
28 
26 
28 
28 


REMARKS. 

Injected  intravenously  0003  gram  dried  venom  of  the  Cro- 
talus  adamanteus  dissolved  in  1  c  c  distilled  water. 


Dead.      Heart  arrested  in  diastole  ;    blood  incoagulable  ; 

few  ecchymoses  in  peritoneum. 
The  section  of  the  cord  was  not  quite  complete. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cro- 
talus  adamanteus  dissolved  in  1  c.  c.  distilled  water. 


Dead.     Heart  arrested  in  diastole ;   blood  incoagulable ;  no 
ecchymoses  in  serous  tissues 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cro- 
talus  adamanteus  dissolved  in  1  c.  c.  distilled  water. 


100 


THE    VENOMS    OP    CERTAIN    THANATOPHIDE<E. 


Time. 

Pressure 

min.   sec. 

m.  in. 

1      00 

27 

1      30 

27 

2      00 

27 

2     30 

22 

9     30 

* 

Experiment  No.  39. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal         .  .  . 

44 

10 

44 

20 

56 

30 

62 

40 

60 

1     00 

52 

1     20 

44  ' 

1     40 

44 

2     00 

38 

4     00 

30 

6     00 

28 

8     00 

26 

12     00 

22 

Experiment  No.  40. 

Time. 

Pressure 

min.   sec. 

m.  m. 

Normal          .  . 

46 

20 

40 

30 

48 

40 

44 

1     00 

44 

1     30 

40 

1     50 

38 

4     20 

28 

6     20 

28 

8     20 

28 

10     20 

28 

12     20 

28 

15     20 

28 

18     20 

28 

21     20 

Experiment  No.  41. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal          .  .   . 

64 

10 

56 

20 

54 

40 

48 

REMARKS. 


Dead.  Heart  arrested  in  diastole ;  blood  incoagulable , 
ecchymoses  well-marked  in  peritoneum  and  pericardium ; 
intestines  congested  ;  50  c.  c  serum  in  peritoneal  cavity. 
Section  of  cord  complete,  except  anterior  columns. 


REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the  Cro- 
talus  horridus  dissolved  in  1  c.  c.  distilled  water. 


Dead. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 

trodon  piscivorus  dissolved  in  1  c.  c.  distilled  water. 
Muscular  movements. 


Dead.      Blood    is   incoagulable;    no    ecchymoses    in   serous 
membranes. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Ancis- 
trodon  contortrix  dissolved  in  1  c.  c.  distilled  water. 


THE    ACTION    OF    VENOMS    UPON    ARTERIAL   PRESSURE.      101 


Time  : 

Pressure 

min. 

sec. 

m.  m. 

1 

00 

42 

1 

30 

40 

2 

00 

42 

4 

00 

50 

1 

00 

56 

9 

00 

54 

11 

00 

48 

13 

00 

48 

15 

00 

48 

17 

00 

48 

20 

00 

48 

22 

00 

48 

22 

15 

38 

22 

30 

32 

REMARKS. 


Experiment  No.  42. 


Normal 


Time  : 
min.   sec 


10 
30 
00 
00 

00 


8  00 

11  00 

14  00 

19  00 


Pressure 
m.  m. 

56 
60 
56 
52 
48 
48 
52 
58 
60 
62 


Injected  0.006  gram. 


Dead. 


REMARKS. 

Injected  intravenously  0.003  gram  dried  venom  of  the  Cobra 
dissolved  in  1  c.  c.  distilled  water  and  a  few  crystals  of 
sodic  chloride  and  filtered. 


Animal  killed  by  pithing. 


To  recapitulate  the  actions  of  pure  venoms  upon  the  arterial  pressure — we  find 
that  the  injection  of  venom  subcutaneously  causes  a  progressive  fall  of  blood 
pressure ;  Avhen  injected  intravenously,  there  is  a  sudden  and  decided  fall  of 
pressure,  which  may  be  immediately  followed  by  death,  or  by  a  gradual  rise,  to 
be  in  turn  succeeded  by  a  decline  with  feeble  pulse  as  death  approaches.  In  the 
Cobra  there  is  a  tendency  to  a  rise  of  pressure,  which  may  go  above  the  normal  as 
death  appears. 

After  section  of  the  pneumogastric  nerves  and  its  depressor  fibres  we  find  no 
alterations  in  the  results  obtained  in  normal  animals,  but  when  section  of  the 
cord  is  made  in  the  middle  or  upper  cervical  region  by  which  the  vaso-motor  centres 
in  the  medulla  oblongata  are  practically  destroyed,  or  when  accompanying  this 
section  the  nerves  in  the  neck  and  the  spinal  cord  in  the  middle  cervical  region 
are  also  cut,  thus  practically  isolating  the  vaso-motor  centres  in  the  medulla  and 
cutting  off  all  central  nervous  connection  with  the  heart,  we  find  that  the  primary 
profound  diminution  of  pressure  is  not  so  marked.  There  may  even  appear  to  be  a 
slight  tendency  on  the  part  of  the  arterial  pressures  to  rise  above  the  normal  just 
before  death.  Even  after  section  of  the  spinal  cord,  as  above,  we  find  in  Cobra 
the  increase  of  pressure  occurring  before  death  as  in  normal  animals. 

These  results  indicate  that  the  primary  positive  failure  of  pressure  is  due  chiefly 


102 


THE    VENOMS    OJP    CERTAIN    THANATOPHIDEJ3. 


to  a  depressant  action  of  the  venom  upon  the  vaso-motor  centres  in  the  medulla 
oblongata,  and  slightly  upon  the  heart.  The  tendency  to  a  rise  of  pressure,  as  well 
as  the  ultimate  fall,  must  be  due  to  some  action  upon  the  heart  itself  or  the  general 
systemic  capillaries.  It  seems  probable  that  the  rise  of  pressure  in  these  experi- 
ments is  of  capillary  origin  since  the  pulse-curves  do  not  indicate  increased  heart 
power,  and  we  have  already  had  reason  to  believe  that  venom  exerts  a  decided 
action  upon  the  capillaries  themselves  to  bring  about  the  remarkable  ecchymoses 
found  so  commonly  in  cases  of  poisoning — an  instance  also  of  peripheral  irritation, 
applicable  here,  is  the  effect  of  venom  on  the  vagi  peripheries  in  causing  an  in- 
creased respiration  rate.  The  ultimate  fall  of  pressure  seems  to  be  cardiac  in 
origin,  since  there  is  an  accompanying  diminution  in  the  force  of  the  beats. 


SECTION  II. — THE  ACTION  OF  VENOM  GLOBULINS  UPON  THE  BLOOD  PRESSURE. 

The  Action  of  Venom  Globulins  upon  the  Blood  Pressure  of  Normal  Animals. — 
Thirteen  experiments  were  made  with  the  globulins  upon  normal  animals.  The 
doses  usually  given  were  those  representing  the  amount  of  globulin  in  0.015 
gram  of  dried  venom.  The  results  of  all  of  these  experiments  indicate  that  all 
the  globulins  exert  an  action  analogous  to  that  of  the  pure  venom,  but  that  they 
exhibit  a  material  difference  in  the  relative  degree  of  their  toxicity. 

Of  the  thirteen  experiments,  seven  were  made  with  the  water-venom-globulin, 
two  with  the  copper-venom-globulin,  and  four  with  the  dialysis-venom-globulin.  Of 
the  first  series,  five  were  made  with  the  globulin  from  the  Crotalus  adamanteus  ;  one 
with  that  of  the  Ancistrodon  piscivorus,  and  one  with  that  of  the  Cobra.  The  second 
and  third  series  were  made  with  globulins  from  the  Crotalus  adamanteus  venom. 

The  water-venom-globulin  produces  the  most  profound  changes,  causing  a  primary 
diminution  of  pressure  almost  equalling  that  produced  by  pure  venom,  while 
dialfjsis-venom-globidin  comes  next;  the  copper-venom-globulin  has  but  little 
effect.  The  actions  of  all  of  these  globulins  is  to  cause  a  primary  fall  of  pressure, 
which  is  followed  by  a  rise  towards  the  normal  and  more  or  less  well  marked, 
while  if  the  dose  is  sufficiently  large  the  rise  is  followed  by  a  fall  to  zero  at  death. 

In  one  experiment  made  with  the  globulin  from  0.035  gram  of  dried  Cobra 
venom  there  was  no  appreciable  effect.  This  was  probably  due  to  the  very  small 
proportion  of  globulin  in  this  variety  of  venom. 


Experiment 

No.  43. 

Time: 

iiiin.    sec. 

Normal 

... 

10 

20 

40 

1     00 

1     30 

3     00 

5     00 

1     00 

Pressure 
m.  m. 
110 

80 

92 

90 

84 

84 

95 

96 
104 


REMARKS. 

Injected  intravenously  0.0012  gram  water-venom-globulin 
(=  0.015  gram  dried  venom)  from  the  dried  venom  of  the 
Crotalus  adamanteus. 


THE    ACTION    OF    VENOMS    UPON    ARTERIAL    PRESSURE.      103 


time: 

Pressure 

inin.    .-IT. 

m.  in. 

9     00 

106 

12     00 

106 

15     00 

110 

18     00 

116 

25     00 

124 

35     00 

130 

45     00 

130 

55     00 

130 

Experiment  No.  44. 

Time  : 

Pressure 

min.   see. 

m.  m. 

Normal 

•    •    • 

130 

10 

... 

20 

96 

40 

96 

1     00 

94 

1     20 

90 

1     40 

90 

3     40 

94 

5     40 

102 

7     40 

108 

9     40 

108 

10     00 

104 

10     20 

104 

10     40 

104 

14     00 

100 

17     00 

106 

20     00 

108 

30     00 

102 

Experiment  No.  45. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal 

.    .    . 

120 

10 

86 

20 

96 

30 

86 

50 

90 

1      10 

84 

4     10 

90 

4     30 

80 

4     35 

104 

4     40 

100 

4     50 

82 

15 

•    •    • 

REMARKS. 


Animal  killed  by  pithing.  Heart  in  diastole ;  some  ecchy- 
moses  in  small  intestine;  blood  remains  fluid  at  the  end  of 
twenty-four  hours — a  few  very  soft  clots  are  found. 


REMARKS. 


Injected  intravenously  the  water-venom-globulin  from   0.03 

gram  dried  venom  of  the  Crotalus  adamanteus. 
Pressure  falling. 


Clot  formed  in  the  canula. 

Injected  water-venom-globulin  from  0.015  gram  dried  venom. 


Animal  killed  by  pithing. 


REMARKS. 

Injected  intravenously  0.0033  gram  water-venom-globulin 
(~  0.045  gram  dried  venom)  from  the  dried  venom  of  the 
Crolalus  adamanleus  dissolved  by  the  addition  of  a  trace 
of  sodic  carbonate. 


Injected  0.0066  gram  as  in  the  foregoing. 


Injected  a  similar  dose. 

Killed  by  pithing.     Heart  arrested  in  diastole ;   few  ecchy- 
moses ;  blood  remains  fluid  after  twenty-four  hours. 


104 


THE  VENOMS  OF  CERTAIN  TH  AN  ATO  P  HIDE^E. 


Experiment  No.  46. 


Time: 

Pressure 

niin.  sec. 

m.  m. 

Normal 

•  •  . 

148 

10 

120 

20 

116 

30 

116 

50 

100 

1  00 

92 

1  30 

82 

3  30 

86 

5  30 

96 

1  30 

106 

9  30 

118 

12  30 

122 

14  30 

126 

16  SO 

124 

17  30 

100 

19  30 

128 

21  30 

132 

26  00 

128 

28  00 

130 

30  00 

124 

30  15 

136 

35  00 

134 

37  00 

136 

39  00 

130 

Experiment  No.  47. 

Time: 

Pressure 

inin.  sec. 

m.  m. 

Normal 

... 

132 

30 

126 

50 

124 

1  00 

136 

1  30 

122 

1  50 

114 

2  00 

106 

2  40 

116 

3  10 

104 

Experiment  No.  48. 

Time: 

Pressure 

min.  sec. 

m.  rn. 

Normal 

.  .  . 

115 

0 

•  .  * 

10 

•  • 

20 

90 

30 

93 

1  30 

90 

2  30 

100 

5  30 

102 

10  30 

100 

14  30 

100 

19  30 

103 

REMARKS. 


Injected    intravenously  the   water-venom-globulin  from   one 
minim  of  fresh  venom  of  the  Crolalus  adamanleus. 


Clot  in  canula. 


Clot  in  canula. 


Animal  killed  by  pithing  ;  no  ecchymoses ;  blood  clots. 


REMARKS. 

Injected  intravenously  the  water-venom-globulin  from  0.004 
gram  dried  venom  of  the  Ancistrodon  piscivorus  dissolved 
in  1  c.  c.  distilled  water  by  the  addition  of  a  few  crystals  of 
sodic  chloride. 

Injected  a  similar  dose. 


REMARKS. 

Injected  intravenously  the  water-venom-globulin  from  0.015 
gram  dried  venom  of  the  Crotalus  adamanleus. 


Hasmaturia. 


THE   ACTION    OF    VENOMS    UPON    ARTERIAL    PRESSURE.      105 


Time  : 

Pressure 

min.    M'C. 

in.  in. 

24     30 

95 

29     30 

85 

34     30 

80 

42     30 

75 

47     30 

73 

52     30 

60 

57     30 

60 

67     30 

57 

77     30 

55 

80     30 

38 

85 

Experiment  No.  49. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal 

.    .    . 

155 

0 

.  .  . 

15 

... 

25 

158 

45 

160 

1     15 

158 

2     00 

157 

4     00 

153 

8     00 

153 

13     00 

153 

18     00 

143 

23     00 

153 

28 

Exjwiment  No.  50. 

Time: 

Pressure 

miu.   sec. 

m.  m. 

Normal 

•    .    . 

126 

10 

126 

20 

126 

30 

132 

50 

126 

2     50 

124 

4     50 

126 

6     50 

126 

8     50 

124 

10     50 

124 

11     50 

120 

17     20 

110 

18     20 

114 

18     30 

110 

18     40 

118 

18     50 

112 

19     00 

112 

20     00 

120 

22     00 

116 

27 

•    .    . 

REMARKS. 


Dead  ;  eccliymoses  in  intestines  ;  blood  incoagulable. 


REMARKS. 

Injected  intravenously  waler-venom-globulin  from  0.035  gram 
dried  Cobra  venom  dissolved  in  1  c.  c.  distilled  water. 


Broke  loose  from  canula. 


REMARKS. 


Injected  intravenously  0.0012  gram  copper-venom-globulin 
(=  0.015  gram  dried  venom)  from  the  dried  venom  of  the 
Crolalus  adamanteus. 


Injected  double  the  foregoing  dose. 


Killed.    Heart  in  systole ;  few  eccliymoses  in  lungs  and  intes- 
tines ;  blood  remains  fluid  after  two  hours. 


14       June.  1886. 


106 


THE   VENOMS   OF   CERTAIN    Til  A  N  A  T  0  P  II I  D  E  M. 


Experiment  No.  51. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

112 

10 

114 

30 

110 

1  00 

112 

3  00 

116 

5  00 

120 

7  00 

122 

8  00 

122 

10  00 

124 

12  00 

118 

22  00 

118 

24  00 

128 

26  00 

124 

26  10 

124 

26  30 

116 

26  40 

104 

27  00 

108 

27  30 

96 

29  30 

90 

31  30 

98 

34  30 

104 

39  00 

116 

41  00 

116 

43  00 

116 

45  00 

118 

52  00 

120 

58  00 

122 

Experiment  No.  52. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

... 

132 

20 

124 

40 

112 

50 

116 

1  20 

108 

3  20. 

108 

5  20 

120 

18  20 

130 

18  23 

... 

18  30 

96 

18  45 

100 

19  05 

94 

19  25 

102 

19  55 

96 

20  25 

76 

20  55 

60 

21  25 

46 

22  00 

42 

30  00 

•  .  * 

REMARKS. 

Injected  intravenously  0.0023  gram  copper-venom-globulin 
(=  0.03  gram  dried  venom)  from  the  dried  venom  of  the 
Crotalus  adamanteus. 


Clot  in  canula. 


Injected  double  the  dose. 


Killed  by  pithing  ;  no  ecchymoses. 


REMARKS. 

Injected  intravenously  0.0017  gram  dialysis-venom-globulin 
from  the  dried  venom  of  the  Crotalus  adamanteus  dissolved 
in  1  c.  c.  distilled  water  with  a  trace  of  sodic  carbonate. 


Injected  0.0034  gram  dialysis-venom-globulin. 


Dead.      No  ecchymoses ;    heart  in  diastole ;    blood   remains 
fluid  at  the  end  of  one  hour. 


THE   ACTION    OF    VENOMS    UPON    ARTERIAL   PRESSURE.      107 


Experiment  No.  53. 

Time  : 

Pressure 

min.  sec. 

m.  m. 

Normal 

126 

20 

120 

30 

114 

1  00 

110 

1  20 

102 

1  40 

104 

2  00 

100 

2  40 

100 

3  40 

102 

5  40 

110 

(J  20 

114 

C  50 

118 

7  20 

124 

1  50 

126 

8  50 

128 

9  20 

128 

9  50 

130 

10  50 

134 

11  50 

122 

12  50 

112 

14  20 

112 

14  50 

84 

15  20 

78 

15  50 

62 

Experiment  No.  54. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

.  .  . 

150 

10 

118 

20 

130 

30 

118 

1  00 

116 

3  00 

110 

5  00 

12(5 

7  00 

124 

ir>  oo 

136 

17  30 

116 

17  40 

100 

18  30 

104 

20  30 

126 

23  30 

118 

28  30 

102 

43  30 

98 

53  30 

94 

REMARKS. 


Injected  intravenously  dialysis-venom-globulin  from  the  dried 
venom  of  the  Crolalttt;  adamanltius  (quantity  unknown). 


•Injected  more  of  the  globulin. 


Killed  by  pithing. 


REMARKS. 

Injected  intravenously  0.0017  gram  dialysis-venom-globulin 
from  the  dried  venom  of  the  Crolalus  adamanteus. 


Injected  0.0034  gram. 


Animal  killed. 


T7te  Action  of  Venom  Globulins  upon  the  Blood  Pressure  of  Animals  in  which 
the  Pneumogastric  Nerves  had  been  /Severed. — Four  experiments  were  made  on 
animals  in  which  the  pneumogastric  nerves  and  depressor  nerves  were  severed. 
The  results  in  these  experiments  do  not  differ  in  quality  from  those  obtained  in 


108 


THE    VENOMS   OF    CERTAIN   THANATOPHIDE^E. 


normal  animals  ;  the  effects,  however,  appear  to  be  less  decided  than  in  animals 
with  the  pneumogastrics  intact.  Here,  as  in  the  previous  experiments,  the  copper- 
venom-globulin  exhibits  comparatively  little  effect  on  the  pressure. 

Of  the  four  experiments  which  were  made  with  globulins  from  the  Crotahis 
adamanteus,  one  was  made  with  the  tcater-venom-i/iolulin ;  two  with  the  copper- 
venom-globulin,  and  one  with  the  dialysis-venom-globulin.  It  will  be  noticed  that  in 
several  instances  considerable  rises  of  pressure  occurred  accompanied  by  struggles ; 
the  former  effect  being,  no  doubt,  due  to  the  latter,  and  not  to  a  peculiar  action 
of  the  globulin. 


Experiment  No.  55. 


Normal 


Time  : 

Pressure 

inin.   sec. 

m.  m. 

.    .    . 

116 

10 

100 

20 

100 

30 

110 

1     00 

106 

1     40 

110 

3     40 

110 

5     40 

108 

Experiment  No.  56. 


Normal 


Time  : 

Pressure 

inin. 

sec. 

m.  m. 

.  . 

. 

130 

10 

132 

20 

132 

30 

132 

40 

132 

1 

10 

132 

3 

10 

132 

5 

10 

128 

7 

10 

128 

9 

10 

128 

23 

10 

136 

23 

20 

130 

23 

40 

132 

23 

55 

132 

24 

00 

116 

24 

15 

116 

Experiment  No.  57. 


Normal 


Time: 
min.   sec. 

20 
40 
50 

2  50 
4  50 
6  50 
8  50 


Pressure 
m.  m. 
116 
116 
116 
116 
116 
116 
116 
112 


REMARKS. 

Injected  intravenously  0.0011  gram  water-venom-globulin  from 
the  dried  veuom  of  the  Crolalus  adamanteus. 


Clot  in  canula.     Animal  killed  by  pithing. 


REMARKS. 

Injected   intravenously  0.0024  gram    copper-venom-globulin 
from  the  dried  venom  of  the  Crotalus  adamanleus. 


Injected  a  similar  dose. 


Respiration  greatly  slowed. 

Animal  broke  loose.     Killed  by  pithing. 


REMARKS. 

Injected  intravenously  0.0012  gram  copper-venom-globulin 
from  the  dried  venom  of  the  Crotalus  adamanteus. 


THE  ACTION  OF  VENOMS  UPON  ARTERIAL  PRESSURE.   109 


Time:  Pressure  REMARKS. 

rniu.  see.  in.  in. 

11  50  116 

13  50  118 

15  50  118         Injected  a  double  quantity. 

16  10  100 

16  20  118  "  "  " 

16  30  110 

16  45  108 

17  45  132        Struggles. 
19  45  114 

21  45  112 

23  45  106 

25  45  100 

26  45  88 

27  00  ...         Animal  killed  by  pithing. 


Experiment  No.  58. 

Time: 

min. 

sec. 

Normal 

10 

20 

30 

50 

1 

50 

4 

20 

6 

20 

8 

20 

10 

20 

12 

20 

17 

50 

18 

20 

18 

30 

18 

40 

19 

00 

19 

15 

19 

20 

21 

50 

22 

00 

23 

00 

25 

00 

27 

00 

29 

00 

34 

00 

34 

30 

38 

30 

41 

00 

47 

00 

49 

00 

Pressure 
m.  m. 

120 
100 
112 

*150 
190 
130 
120 
126 
122 
120 
118 
118 
100 
148 
140 
170 
176 
144 
140 
166 
122 
128 
114 

82 

80 

60 

50 

28 


REMARKS. 

Injected  intravenously  0.0017  gram  dialysis -venom-globulin 
from  the  dried  venom  of  the  Crotalus  adamanleus. 


Struggles. 


Injected  0.0034  gram. 

Struggles.     Injected  a  similar  dose. 


Struggles. 


Dead. 


The  Action  of  Venom  Globulins  upon  the  Blood  Pressure  of  Animals  in  «?/</>•// 
the  Pneumogastric,  Depressor,  and  Sympathetic  Nerves  and  Cervical  Spinal  Cord 
had  been  Cut. — Four  experiments  were  made  on  animals  in  which  the  nerves  of  the 


110 


THE   VENOMS   OF   CERTAIN   T  II  AN  A  T  0  PII I  D 


neck  and  the  cord  in  the  middle  or  upper  cervical  region  (excepting  one)  were  cut. 
They  were  all  made  with  the  globulins  from  the  Crotalus  adamanteus ;  one  with 
water-venom-globulin,  one  with  copper-venom-globulin,  and  two  with  dialysis-venom- 
globulin. 

The  results  of  this  series  of  experiments  accord  with  those  observed  when  pure 
venom  was  used,  and  with  the  preceding  experiments  with  the  globulins.  The 
primary  fall  of  pressure  is  slight,  while  the  tendency  to  a  secondary  rise  is  very 
marked,  since  in  three  of  the  experiments  the  pressure  rose  above  the  normal. 
The  action  of  water-venom-globulin  on  the  primary  fall  was  most  marked,  while  in 
the  single  experiment  made  with  copper-venom-globulin,  in  which  eight  times  the 
quantity  was  given  in  two  doses,  the  pressure  rose  slightly,  and  continued  above 
normal.  When  the  dose  is  sufficient  to  kill,  the  pressure  ultimately  gradually 
declines,  accompanied  by  a  feeble  pulse. 

In  the  last  experiment  with  dmlt/sis-venom-glolulin  it  will  be  noticed  that 
tremors  are  accompanied  with  a  rise  of  pressure  during  their  existence. 


Experiment  No.  59. 


Normal 


Time: 
m In.   sec. 

10 


Pressure 

m.  m. 

48 

38 


30 

38 

1 

00 

48 

1 

10 

34 

2 

10 

46 

3 

10 

42 

5 

10 

40 

1 

10 

38 

9 

10 

34 

11 

10 

30 

15 

10 

30 

17 

40 

30 

19 

00 

30 

21 

00 

30 

23 

00 

30 

25 

00 

30 

27 

00 

30 

REMARKS. 

Section  of  cord  made  below  the  6th  cervical  vertebra.  Injected 
intrav.enously  0.0011  gram  ivater-venom-ylobulin  from  the 
dried  venom  of  the  Crolalus  adamanteus. 

Artificial  respiration  stopped. 


Animal  killed  by  pithing. 


Experiment  No.  60. 


Normal 


Time: 
inin.   sec. 

10 
20 
40 

1  00 
3  30 
5  30 
7  30 


Pressure 
m.  m. 

29 
32 
30 
32 
32 
38 
40 
42 


REMARKS. 

Injected   intravenously  0.0048   gram  copper-venom-globulin 
from  the  dried  venom  of  the  Crotalus  adamanteus. 


THE  ACTION  OF  VENOMS  UPON  ARTERIAL  PRESSURE.   HI 


Time: 

Pressure 

mill.   sec. 

m.  m. 

9     30 

42 

11     30 

42 

13     30 

40 

1C     30 

44 

17     00 

42 

17     30 

38 

18     00 

40 

20     00 

44 

24     00 

46 

26     00 

44 

28     00 

42 

30     00 

40 

32     00 

40 

34     00 

40 

Experiment  No.  61. 

Time  : 

Pressure 

miu.   sec. 

m.  m. 

Normal 

42 

10 

40 

30 

40 

1     00 

46 

3     00 

44 

6     00 

40 

8     30 

38 

10     30 

38 

12     30 

.    .    . 

12     50 

44 

13     10 

48 

13     30 

46 

13     50 

48 

15     00 

36 

16     00 

46 

18     00 

28 

Experiment  No.  62. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

.    .    . 

44 

10 

40 

20 

40 

30 

44 

40 

52 

50 

62 

1     00 

62 

1      10 

60 

1     20 

58 

3     20 

86 

3     50 

52 

6     50 

22 

8     50 

8 

9     00 

.    «    . 

REMARKS. 


Injected  a  similar  quantity. 


Animal  killed  by  pithing. 


REMARKS. 

Injected   intravenously  0.0017  gram  dialysis-venom-globulin 
from  the  dried  venom  of  the  C'rolalun  adamanteus. 


Injected  0.0068  gram. 


Dead.  Heart  arrested  in  diastole;  no  ecchymoses ;  blood 
fluid.  A  few  fibres  of  the  anterior  columns  of  the  cord  were 
uncut. 


REMARKS. 

Injected   intravenously  0.0068  grain  dialysis-venom-globulm 
from  the  dried  venom  of  the  Crotalus  adamanleus. 


Universal  tremors  persistent. 


Clot  in  canula. 

Blood  pressure  fell  very  low  before  this  observation,  and  was 
raised  by  the  tremors  returning  vigorously. 


Dead.     No  ecchymoses  ;  blood  incoagulable  ;   heart  natural. 


112 


THE    VENOMS    OF    CERTAIN    T  II  A  N  A  T  0  PH  I  D  E  JR. 


From  this  series  of  experiments  with  globulins  it  seems  clear  that  they  possess 
the  peculiar  physiological  effects  of  pure  venoms  upon  the  blood  pressure;  that  the 
water-venom-globulin  is  the  most  powerful,  and  the  copper-venom-globulin  the 
least  so,  and  that  the  copper-venom-globulin  seems  to  exhibit  a  more  marked 
tendency  than  the  others  to  cause  a  rise  of  pressure. 


SECTION  III. — THE  ACTION  OF  VENOM  PEPTONES  UPON  THE  BLOOD  PRESSURE. 

The  Action  of  Venom  Peptones  upon  the  Blood  Pressure  of  Normal  Animals. — 
Seven  experiments  were  made  with  the  peptones  from  different  venoms :  two  with 
that  of  Crotalus  adamanteus ;  three  with  Ancistrodon  piscivorus  ;  and  two  with 
Cobra.  The  action  of  peptones  upon  the  blood  pressure  is  similar  to  that  observed 
with  the  pure  venom  and  the  globulins,  but  their  power  to  cause  the  primary  pro- 
found fall  of  pressure  is  certainly  much  less,  while  the  rise  of  pressure  after  the 
primary  fall  is  decidedly  more  marked,  and  there  is  also  a  tendency  to  go  above  the 
normal.  In  two  experiments,  one  with  the  peptone  of  the  Crotalus  and  one  with 
that  of  the  Moccasin,  the  pressure  was  not  primarily  reduced,  but  there  was  a  rise 
above  the  normal  from  the  first.  Where  the  animal  was  watched  until  death  the 
pressure  was  observed  to  undergo  a  more  or  less  gradual  decline  with  feeble  heart- 
beats. In  several  instances  a  rise  of  pressure  was  noted  which  was  usually  due  to 
convulsive  seizures. 


Experiment  No.  63. 


Normal 


Time: 

Pressure 

min. 

sec. 

m.  m. 

. 

140 

10 

128 

20 

128 

30 

136 

40 

128 

50 

128 

1 

00 

124 

11 

00 

116 

21 

00 

116 

49 

•     •    * 

REMARKS. 

Injected   intravenously  the  peptone  from   0.015  gram  dried 
venom  of  the  Crotalus  adamanteus. 


Experiment  No.  64. 


Normal 


Time: 
min.   sec. 


10 

30 

00 
00 
00 


9     00 


Pressure 
m.  m. 
114 
130 
132 
120 
140 
144 
124 


Clot. 

Dead.     No  ecchymoses ;  lungs  seem  congested  ;  blood  clots 
readily. 


REMARKS. 

Injected    intravenously  the  peplone  from   0.03  gram   dried 
venom  of  the  Crotalus  adamanteus. 


Killed.     Ecchymoses  in  the  lungs  ;  blood  clots. 


THE    ACTION    OF    VENOMS    UPON  ARTERIAL   PRESSURE.      113 


Experiment  No.  65. 


Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal 

.    .    . 

86 

30 

88 

1     00 

88 

1     30 

88 

4     30 

92 

10     30 

94 

10     50 

100 

11     10 

102 

11     30 

96 

Experiment  No.  66. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal 

... 

116 

10 

94 

20 

66 

30 

70 

1     00 

76 

1     30 

74 

2     00 

76 

2     30 

76 

3     00 

76 

5     00 

66 

5     20 

60 

5     40 

66 

6     00 

68 

6     30 

66 

7     00 

62 

7     30 

56 

8     00 

60 

Experiment  No.  67. 

Time: 

Pressure 

min.  sec. 

m.  in. 

Normal 

.    .    . 

140 

10 

94 

20 

100 

30 

160 

40 

170 

50 

190 

1     00 

130 

1     20 

130 

1     40 

142 

2     00 

136 

2     20 

136 

2     40 

136 

5     40 

118 

5     50 

114 

6     00 

104 

6     20 

112 

6     30 

112 

9     30 

118 

13     30 

122 

15 

June,  1886. 

REMARKS. 


Injected    intravenously  the  peptone  from  0.015   gram  dried 
veuotu  of  the  Ancistrodon  pisciuorus. 


Injected  double  the  amount. 


REMARKS. 


Injected   intravenously  the  peptone  from  0.015  gram  dried 
venom  of  the  Aneittrodon  piscivorus. 


Injected  a  similar  quantity. 


Injected  a  double  quantity. 


REMARKS. 

Injected   intravenously  the  peptone  from   0.05   gram   dried 

venom  of  the  Ancistrodon  piscivorus. 
Convulsions. 


Injected  0.005  peptone. 


Killed. 


114 


THE    VENOMS    OF    CERTAIN    T U A N A T 0 P H I D E M. 


Experiment  No.  68. 


Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

.  .  . 

140 

10 

130 

20 

148 

30 

140 

40 

142 

1  00 

142 

1  20 

140 

3  20 

138 

6  20 

152 

11  20 

224 

16  20 

176 

16  50 

134 

17  50 

92 

18  20 

]04 

18  50 

84 

19  00 

46 

19  10 

46 

19  30 

38 

19  SO 

36 

20  10 

40 

20  30 

40 

Experiment  No.  69. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

.  .  . 

130 

10 

130 

15 

116 

30 

156 

50 

156 

3  20 

140 

8  20 

190 

10  20 

176 

10  30 

208 

10  40 

182 

10  50 

136 

11  00 

116 

11  20 

102 

11  40 

86 

12  00 

66 

12  20 

54 

12  40 

38 

REMARKS. 

Injected   intravenously   the  peptone  from  0.005  gram  dried 
Cobra  venom. 


Convulsive  twitchings. 


Blood  is  asphyxiated  ;  no  respiration. 


Killed. 


REMARKS. 

• 

Injected   intravenously  the  peptone  from  0.06   gram   dried 
Cobra  venom. 


Tonic  convulsions. 
Convulsive   twitchings ; 
ceased. 


asphyxiated    blood ;    respiration 


Dead. 


The  Action  of  Venom  Peptones  on  the  Blood  Pressure  of  Animals  with  Pneumo- 
gastric  and  Depressor  Nerves  Severed. — After  section  of  the  pneumogastric  and 
depressor  nerves  the  results  are  not  appreciably  altered.  Four  experiments  were 
made:  one  with  Crotalus  adamanteus  ;  one  with  Ancistrodon  piscivorus,  and  two 
with  Cobra  venom.  In  all  of  these  experiments  the  pressure  during  the  secondary 
rise  went  above  the  normal. 


THE    ACTION    OF    VENOMS    UPON    ARTERIAL    PRESSURE.      115 


Experiment  No.  70. 

Time  : 

Pressure 

miii.  sec. 

m.  111. 

Normal          .  .  . 

160 

10 

160 

15 

140 

30 

150 

40 

156 

50 

156 

1     00 

134 

1     20 

158 

1     30 

164 

3     30 

126 

8     30 

122 

5     30 

146 

20     30 

148 

25     30 

140 

30     30 

140 

35     00 

136 

40     00 

148 

45     00 

142 

50     00 

140 

62     00 

138 

Experiment  No.  71. 

Time  : 

Pressure 

min.   sec. 

m.  m. 

Normal          .  .   . 

124 

10 

100 

20 

140 

30 

150 

40 

130 

50 

140 

1     00 

134 

1      20 

114 

1     40 

116 

2     00 

136 

2     30 

124 

2     40 

110 

2     50 

124 

3     00 

136 

3     10 

110 

3     2(1 

96 

4     20 

Experiment  No.  72. 

Time  : 

Pressure 

min.   sec. 

m.  in. 

Normal          .  .   . 

138 

10 

142 

20 

136 

40 

134 

1     00 

140 

1     30 

138 

REMARKS. 

Injected   intravenously  the  peptone  from  0.015  gram  dried 
venom  of  the  Crotalus  adamanteus. 


Struggles. 


Struggles. 


Killed. 


REMARKS. 


Injected  intravenously  the   peptone  from  0.015  gram  dried 
venom  of  the  Ancistrodon  piscivorus. 


Respiration  ceased ;  heart  beats. 


REMARKS. 


Injected   intravenously  the  peptone  from  0.005  gram  dried 
Cobra  venom. 


116 


THE    VENOMS    OF    CERTAIN    THAN  ATOP  II 


Time  : 

Pressure 

min.    sec. 

m.  m. 

3      30 

136 

5      30 

136 

7     30 

132 

9     30 

132 

10     00 

140 

21     30 

146 

25     30 

142 

26     30 

150 

Experiment  No.  73. 

Time: 

Pressure 

min.  sec. 

m.  m. 

Normal 

.    . 

124 

10 

122 

20 

128 

40 

124 

1     00 

126 

3     00 

120 

5     00 

120 

16     00 

118 

34     00 

• 

REMARKS. 


Twitchings. 

Killed.     No  ecdiymoses. 


REMARKS. 

Injected  intravenously  the  peptone  from  0.006   gram  dried 
Cobra  venom. 


Dead.     Asphyxiated;  no  ecchymoses ;  blood  clots  in  canula. 


The  Action  of  Venom  Ptplones  en  tJie  Blood  Pressure  of  Animals  in  which  the 
Pneumofjastric,  Depressor,  and  Sympathetic  Nerves  and  Cervical  Spinal  Cord  were 
Cut. — In  five  experiments  on  animals  in  which  the  nerves  in  the  neck  and  the 
spinal  cord  in  the  middle  or  upper  cervical  region  were  cut  we  found  that  but  little 
alteration  occurred  in  the  blood  pressure  until  late  in  the  poisoning,  excepting  in 
one  experiment  with  the  Ancistrodon  piscivorw,  in  which  the  pressure  sunk  imme- 
diately and  death  occurred  in  thirty  seconds.  Two  experiments  were  made  with 
the  peptone  of  the  Crotalus  adamantens ;  one  with  the  Ancistrodon  piscivorus,  and 
two  with  the  Cobra.  In  all  of  these  experiments,  excepting  one  with  Cobra,  there 
was  an  immediate  comparatively  slight  fall  of  pressure  after  injection,  which  was 
followed  generally  by  a  rise;  in  the  excepted  case  of  the  Cobra  there  was  a  primary 
rise  equal  to  3  m.  m.  of  mercury,  which  was  followed  by  a  fall,  and  this  in  turn 
by  a  rise.  The  pressure,  as  in  the  previous  experiments,  usually  declines  towards 
death. 


REMARKS. 

Injected  intravenously  the  peptone  from  0.015  gram  dried 
venom  of  the  Crotalus  adamanleus. 


Experiment  No.  74. 

Time: 

Pressure 

min. 

sec. 

m.  m. 

Normal 

50 

10 

50 

20 

48 

40. 

48 

1 

00 

48 

3 

00 

44 

6 

00 

42 

11 

00 

42 

13 

00 

42 

15 

00 

42 

THE    ACTION    OF    VENOMS    UPON    ARTERIAL   PRESSURE.      117 


Time: 

Pressure 

REMARKS. 

min.   6cc. 

m.  in. 

n    oo 

50 

Injected  the  peptone  from  0.03  gram  dried  venom. 

17     30 

50 

19     30 

48 

21     30 

48 

23     30 

46 

25     30 

46 

i 

27     30 

44 

29     30 

44 

31     30 

42 

34     30. 

38 

Dead.     No  ecchymoses  ;  blood  fluid  after  fifteen  minutes. 

Experiment  No.  75. 

Time: 

Pressure 

REMARKS. 

min.   sec. 

m.  m. 

Normal          .  .  . 

67 

Injected  intravenously  the  peptone  from  0.015  gram  dried 

15 

50 

venom  of  the  Crolalus  adamanteus. 

20 

50 

30 

50 

1     00 

50 

1     30 

50 

2     00 

50 

Experiment  No.  76. 

Time  : 

Pressure 

REMARKS. 

min.    sec. 

m.  m. 

Normal          .   .   . 

50 

Injected  intravenously  the  peptone  from  0.015  gram  dried 

10 

45 

venom  of  the  Ancistrodon  piscivorus. 

18 

38 

30 

33 

1     00 

... 

Dead. 

Experiment  No.  77. 

Time: 

Pressure 

REMARKS. 

min.   sec. 

m.  m. 

Normal          .  .   . 

128 

Injected   intravenously  the  peptone   from   0.01    gram  dried 

10 

122 

Cobra  venom. 

20 

132 

30 

134 

1     00 

132 

• 

12     00 

138 

12     30 

136 

17     30 

•    .    • 

Dead.     Blood  clots  readily.     Ecchymoses  in  base  of  lungs. 

118 


THE   VENOMS   OF    CERTAIN   T  H  AN  A  T  0  P  II I D 


Experiment  No.  78. 

Time  : 

min. 

see. 

Normal 

,    . 

11 

20 

40 

1 

40 

5 

40 

10 

40 

15 

40 

16 

00 

1(5 

06 

Ifi 

15 

10 

25 

16 

45 

17 

00 

18 

00 

20 

00 

23 

00 

Pressure 
m.  m. 
38 
39 
41 
40 
35 
35 
37 
38 

38 
38 
43 
43 
43 
40 
25 


REMARKS. 

Injected    intravenously  the   peptone  from  0.015  gram  dried 
Cobra  venom. 


I  Injected  a  similar  dose. 


Dead. 


From  all  of  the  results  of  these  experiments  it  seems  justifiable  to  conclude  that 
the  isolated  principles  of  venoms  exert  the  poisonous  actions  of  pure  venoms  on 
the  blood  pressure,  and  that  their  toxic  effects  are  essentially  simply  different  in 
degree.  These  various  poisons  all  play  a  part  in  the  alterations  of  pressure,  acting 
towards  the  same  end,  but  mainly  with  different  degrees  of  intensity ;  the  water- 
venom-globulin  appears  to  be  the  most  potent  in  the  pressure  alterations,  the  dialy- 
sis-venom-globulin next,  then  the  peptone,  and  finally  the  copper-venom-ylobulin. 
The  globulins  are  the  more  active  in  the  production  of  the  diminution  of  pressure, 
and  the  peptone  in  the  secondary  rise. 

The  globulins  no  doubt  play  a  very  important  part  in  the  poisonous  phenomena 
of  Crotalus  poisoning,  a  less  important  part  in  Ancistrodon  poisoning,  and  but  very 
little  in  Cobra  poisoning;  these  differences  not  depending  as  much  upon  differences 
in  the  quality  of  the  globulins  in  the  species  of  venom  to  which  they  belong  as  on 
differences  in  quantity. 


THE   ACTION    OF    VENOMS    UPON    RESPIRATION. 


119 


CHAPTER    IX. 

THE  ACTION  OF  VENOMS  AND  THEIR  ISOLATED  GLOBULINS  AND 
PEPTONES  UPON  RESPIRATION. 


SECTION  I.  —  PURE  VENOM. 

IN  our  experiments  on  respiration  rabbits  were  always  used,  and  the  rate  of 
breathing  was  recorded  on  a  revolving  drum  by  the  lever  of  a  Marey's  tambour,  the 
latter  being  connected  with  the  animal  by  means  of  a  tracheal  tube.  The  injections 
in  all  of  the  experiments,  excepting  two,  which  were  subcutaneous,  were  made  into 
the  external  jugular  vein. 

In  experiments  on  normal  animals  we  observed  no  qualitative  difference  in  the 
several  venoms  used.  Ten  experiments  were  made  upon  normal  animals  :  four 
with  the  venom  of  the  Crotalus  adamanteus  ;  three  with  that  of  the  Moccasin, 
pisci  corns,  and  three  with  that  of  the  Cobra.  In  eight  of  these  experiments  there 
was  a  primary  increase  in  the  respiration  rate  followed  by  a  diminution  far  below 
the  normal,  while  in  two  the  respirations  were  at  once  diminished,  and  became  per- 
sistently slower  until  death.  In  both  of  these  cases  death  occurred  very  soon  after 
injection,  indicating  a  most  profound  action  of  the  poison. 

Action  of  tlie,  Pure  Venoms  on  the  Respirations  in  Normal  Animals. 


Experiment  No.  1. 

Length  of 
Time :  Respirations          curve 


Normal 


min. 

sec. 

per  minute. 

m.  m. 

84 

10 

10 

180 

1C 

40 

84 

12 

1 

96 

•  •  • 

2 

20 

108 

.  .  . 

4 

50 

72 

8 

6 

50 

72 

6 

8 

50 

60 

6 

10 

50 

48 

.  .  . 

11 

20 

40 

4 

11 

50 

24 

4 

12 

20 

26 

•  .  * 

12 

50 

... 

•  •  • 

REMARKS. 

Injected  intravenously  0.002  gram  dried  venom  of  the 
Grotalus  adamanteus  dissolved  in  1  c.  c.  distilled 
water. 


Convulsive  movements. 


Dead. 


120 


THE  VENOMS  OF  CERTAIN  THAN ATOPHIDE JE. 


Experiment  No.  2. 


Normal 


Length 

Time: 

Respirations 

curve 

min. 

sec. 

per  minute. 

m.  in. 

42 

6 

10 

43 

10 

40 

? 

1 

00 

84 

12 

2 

10 

30 

25 

3 

40 

9 

23 

5 

00 

10 

14 

5 

10 

•    •    * 

f 

of 


Experiment  No.  3. 


Normal 


Length  of 

Time: 

Respirations 

curve 

min 

.  sec. 

per  minute. 

m.  m. 

. 

.    . 

84 

7 

20 

158 

3 

40 

120 

7 

1 

00 

96 

11 

1 

30 

90 

10 

2 

00 

96 

12 

2 

30 

102 

10 

3 

00 

120 

7 

3 

30 

35 

5 

4 

30 

60 

6 

5 

30 

35 

10 

6 

30 

10 

7 

7 

30 

4 

4 

Experiment  No.  4. 


REMARKS. 

Injected  intravenously  0.004  gram  dried  venom  of  the 
Crolalus  adamanleus  dissolved  in  1  c.  c.  distilled 
water. 

Struggles,  which  prevent  a  count. 

Convulsive  movements. 
Conjunctival  reflexes  gone. 

Respiration  ceased.  Heart  still  beating.  The  respira- 
tory muscles  respond  to  stimulus.  The  spinal  cord 
was  exposed,  and  the  motor  columns  were  found  to 
respond  to  electrical  stimulus.  The  motor  nerves 
responded  after  the  motor  columns  of  the  cord  had 
lost  their  irritability. 


REMARKS. 

Injected  intravenously  0.006  gram  dried  venom  of  the 
Crotalus  adamanleus  dissolved  in  3  minims  distilled 
water. 


Time :  Respirations 

min.   sec.  per  minute. 

Normal      ...  66 


15 

30 
00 
50 


36 
12 
18 


2     20 
2     25 


Length 
curve 
m.  ra. 
6 


16 

16 

6 

5 


Struggles. 


Conjunctival  reflexes  gone. 

Respiration  ceased.  Respiratory  muscles  irritable. 
The  spinal  cord  was  quickly  exposed ;  the  sensory 
columns  give  no  response,  the  motor  columns  are 
active.  The  motor  columns  of  the  cord  fail  before 
the  motor  nerves. 


of 


REMARKS. 

Injected  intravenously  0.015  gram  dried  venom  of  the 
Crotalus  adamanleus  dissolved  in  1  c.  c.  distilled 
water. 

Arrest  of  respiration  attended  with  a  tetanic  condition. 


Respiration  ceased.  Spinal  cord  rapidly  exposed  and 
tested  by  electrical  currents;  sensory  columns  fail 
first,  then  the  motor  columns,  then  motor  nerves. 


THE  ACTION  OF  VENOMS  UPON  RESPIRATION. 


121 


Experiment  No.  5. 


J. 

Length  of 

* 

Time  : 

Respirations 

eurve 

REMARKS. 

min.   sec. 

per  minute. 

in.  m. 

Normal      .  .  . 

100 

9 

Injected  intravenously  0.004  pram  dried  venom  of  the 

10 

210 

8 

Ancistrodon  piscivorus  dissolved  iu  5 

minims  dis- 

20 

150 

21 

tilled  water. 

30 

140 

20 

40 

120 

23 

50 

... 

.  .  . 

Convulsions. 

1      10 

Dead. 

Experiment  No. 

6. 

Length  of 

Time  : 

Respirations 

curve 

REMARKS. 

min.   sec 

per  minute. 

m.  m. 

Normal      .  .   . 

135 

6 

Injected  intravenously  0.004  gram.  dried  venom  of  the 

Ancistrodon  piscivorus  dissolved  in  1 

c.  c.  distilled 

water. 

10 

420 

.    .    . 

Struggles.      Respiration   at  once  began 

to  increase 

20 

270 

6 

rapidly,  and  reached  a  maximum  rapidity  during  the 

occurrence  of  struggles. 

30 

65 

18 

Tetanic  movements. 

40 

60 

.  .  . 

a                         if 

50 

120 

10 

1     00 

120 

.  .  . 

<*                         .. 

1     10 

60 

.  .  . 

1     20 

90 

12 

6     20 

60 

.  .  . 

11     20 

180 

.  •  • 

16     20 

210 

.  .  . 

16     30 



Killed. 

Experiment  No. 

7. 

Length  of 

Time  : 

Respirations 

curve 

REMARKS. 

min.    sec. 

per  minute. 

m.  m. 

Normal      .   .  . 

144 

6 

Injected  intravenously  0.004  gram  dried 

venom  of  the 

10 

300 

8 

Ancixtrodon  piscioorus    dissolved  in  1 

c.  c.  distilled 

20 

240 

12 

water. 

30 

150 

11 

5     00 

60 

10 

7     00 

80 

7 

12     00 

54 

7 

18     00 

70 

7 

18     05 

... 

.  .  . 

Injected  as  above  0.008  gram  venom. 

18     30 

210 

9 

18     40 

160 

10 

18     50 

80 

5 

23     50 

65 

7 

Killed  by  pithing. 

16       June,  1886. 


122 


THE   VENOMS  OF   CERTAIN   T  H  A  N  A  T  0  F  H  1 D  E 


Experiment  No.  8. 


Normal 


Time: 
niin.    sec. 

Respirations 
per  minute. 
60 

Length  of 
curve 
m.  m. 
9 

20 

80 

... 

40 

120 

15 

1 

00 

100 

45 

1 

20 

60 

10 

1 

40 

42 

38 

2 

00 

•  •  • 

... 

REMARKS. 

Injected  intravenously  0.015  pram  dried  Cobra  venom 

dissolved  in  1  c.  c.  distilled  water  and  filtered. 
Struggles. 


Respiration  ceased. 


Experiment  No.  9. 


Time  : 
min.  sec. 
Normal      .  .  . 
10 

Respirations 
per  minute. 

300 
300 

Length  of 
curve                                                   REMARKS, 
m.  m. 
8         Injected  intravenously  0.015  gram  dried  Cobra  venom 
9             dissolved  in  1  c.  c.  distilled  water. 

20 

255 

11 

30 

285 

10 

40 

240 

10 

1     00 

255 

11 

1     30 

200 

9 

2     00 

150 

7 

2     10 

125 

7 

8     20 

Respiration  ceased. 

Experiment  No. 

10. 

Time: 
min.  sec. 
Normal      .   .   . 
20 

Respirations 
per  minute. 

36 
39 

REMARKS. 
Injected  intravenously  0.^03  gram  dried  Cobra  venom  in  solution. 

40 

39 

1     00 

51 

1     30 

52 

2     00 

45 

4     00 

48 

9     00 

46 

12     00 

36 

14 

.  .  . 

Respiration  ceased. 

.  TJie  Action  of  Pure  Venoms  on  (lie  Respiration  in  Animals  in  which  tfie  Pneii- 
mocjastric  Nerves  were  Cut. — When  injections  are  made,  after  section  of  the  pneu- 
mogastric  nerves,  the  primary  increase  in  the  respiration  rate  does  not  occur,  but  a 
diminution  begins  at  once;  and,  on  the  whole,  drops  irregularly  until  death  ensues. 
Four  experiments  were  thus  made :  one  with  Crotalus  adamanteus,  two  with 
Ancistrodon  pisdvorus,  and  one  with  Cobra  venom ;  the  results  being  on  the  whole 
reasonably  uniform. 


THE  ACTION  OF  VENOMS  UPON  RESPIRATION. 


123 


Experiment  No.  11. 


J. 

Length  of 

Time: 

Respirations 

curve 

REMARKS. 

niin.   sec. 

per  minute. 

in.  m. 

Normal      .  .  . 

42 

7 

Injected  intravenously  0.002  gram  dried  venom  of  the 

Crotalus  adamanteus  dissolved  in  1  c.  c. 

distilled 

water. 

30 

20 

18 

Slight  struggles  preceding  this  observation  interfered 

1     00 

28 

10 

with  the  marker. 

1     30 

6 

22 

2     00 

6 

19 

2     30 

3 

25 

3     00 

12 

18 

3     30 

6 

21 

4     30 

6 

21 

5     30 

6 

15 

6     30 

8 

12 

Experiment  No. 

12. 

Length  of 

Time  : 

Respirations 

curve 

REMARKS. 

niin.   sec. 

per  minute. 

m.  m. 

Normal      .  .  . 

103 

15 

Injected  intravenously  0.004  gram  dried  venom  of  the 

10 

94 

15 

Ancintrodon  piscivorus  dissolved  in  1  c.  c. 

distilled 

water. 

20 

84 

30 

Struggles. 

30 

102 

25 

40 

77 

25 

50 

60 

28 

1     00 

CO 

25 

1     10 

45 

30 

1     15 

•    •    • 

Dead.    Respiration  ceased  ;  heart  still  beats. 

Animal 

dies  in  tetanus. 

Experiment  No. 

13. 

^ 

Time: 

Respirations 

REMARKS. 

inin.  sec. 

per  minute. 

Normal     .  .  . 

102 

Injected 

intravenously  0.003  gram  dried  Cobra  venom 

dissolved 

30 

57 

in  1  c. 

c.  distilled  water. 

1     00 

78 

2     00 

57 

4     00 

66 

10 

Experiment  No. 

14. 

Length  or 

Time: 

Respirations 

curve 

REMARKS. 

mill.    sec. 

per  minute. 

m.  m. 

Normal      .  .  . 

127 

17 

Injected  intravenously  0.004  gram  dried  venom  of  the 

Ancistrodon  piscivorus  dissolved  in  1  c.  c 

.  distilled 

water. 

20 

92 

47 

30 

90 

32 

40 

82 

.  .  . 

50 

82 

... 

1     05 

67 

... 

1     30 

... 

... 

Respiration  ceased. 

124  THE    VENOMS    OF    CERTAIN    T  II  A  N  A  T  O  P  H  I  D  E  &. 

In  none  of  these  experiments  do  we  find  a  primary  increase  in  the  respiration 
rate,  as  in  animals  with  intact  vagi,  but  invariably  a  diminution.  It  seems  clear, 
therefore,  that  the  first  result  must  be  dependent  upon  an  excitation  of  the  peri- 
pheries of  the  pneumogastric  nerves,  and  that  the  diminution  of  respirations  is 
due  to  a  centrally  active  cause.  Should  the  lessened  number  of  the  respirations  be 
central,  that  is,  dependent  upon  a  depression  of  the  respiratory  centres,  we  would 
expect  to  find  that  the  degree  of  depression  would  depend  upon  the  relative  amount 
of  venom  coming  in  contact  with  these  centres  in  a  given  space  of  time.  We  have 
accordingly  made  an  experiment,  in  which  this  suggestion  is  admirably  carried  out 
by  injecting  the  venom  into  the  carotid  artery,  thus  throwing  the  poison  directly 
upon  the  respiratory  centres. 

Experiment  No.  15. 


Length  of 

Time: 

Respirations 

eurve 

REMARKS. 

min 

.  sec. 

per  minute. 

m.  m. 

Normal 

.    . 

78 

42 

Injected  into  the  right  carotid  artery 

0.015  gram  of 

15 

7 

38 

dried  venom  of  Grotalus  adamanteus 

dissolved  in  1 

30 

4 

30 

c.  c.  distilled  water. 

1 

00 

4 

25 

1 

30 

10 

45 

Convulsions. 

2 

00 

... 

•    •    * 

Dead. 

It  seems  obvious  from  the  preceding  experiments  that  venoms  exert  a  double 
action  on  the  respiration ;  first,  an  irritant  action  on  the  peripheries  of  the  pneu- 
mogastric nerves,  by  which  an  increase  in  the  respiration  rate  is  brought  about ; 
and  secondly,  a  depression  of  the  respiratory  centres,  by  which  the  respiration 
rate  is  diminished.  Since  the  diminution  in  the  respirations  occurs  in  animals  with 
cut  pneumogastrics  immediately  after  injection,  and  at  a  time  when  an  increase 
occurs  in  normal  animals,  it  is  apparent  that  these  two  factors  are  acting  in  normal 
animals  at  the  same  time  to  produce  opposite  results ;  consequently,  whether  we 
have  an  increase  or  a  decrease  in  the  respirations  must  be  dependent  upon  the 
relative  degree  of  power  exerted  by  one  or  the  other  of  these  factors.  In  most 
cases  we  have  found  a  primary  increase  of  respirations  followed  by  a  diminution ; 
it  is  therefore  obvious  that  the  action  of  the  venom  upon  the  peripheries  of  the 
pneumogastric  nerves  was  more  than  able  to  compensate  for  the  depressant  action 
of  the  poison  upon  the  respiratory  centres ;  this  is  very  clear  since  no  increase  of 
respirations  above  normal  occurs  in  animals  with  cut  pneumogastrics.  In  the  two 
cases  in  normal  animals  in  which  a  decline  from  the  first  was  observed,  and  in 
which  the  animals  died  in  a  few  minutes  after  injection,  the  action  of  the  venom 
upon  the  respiratory  centres  was  so  profound  that  the  accelerator  factor  was  unable 
to  cause  a  rise.  This  is  also  illustrated  in  the  experiment  in  which  the  venom  was 
injected  into  the  carotid  artery  and  thrown  upon  the  respiratory  centres. 

Since  venom  does  not  seem  to  exert  other  than  a  depressant  action  upon  the 
respiratory  centres,  it  does  not  appear  probable  that  it  would  have  an  opposite 
effect  upon  the  respiratory  nerves,  so  that  the  effect  of  the  venom  upon  the  peri- 
pheries of  the  pneumogastric  nerves  is  probably  one  of  irritation  rather  than  stimu- 


THE   ACTION    OP   VENOMS   UPON    II  E  S  P  I  It  A  T  ION. 


125 


lation,  and  probably  due  to  some  secondary  cause,  which  is  likely  to  be  located  in 
the  profound  alteration  of  the  blood  or  the  destructive  action  of  the  venom  upon 
the  pulmonary  tissues,  as  illustrated,  for  instance,  upon  capillaries. 


SECTION  II. — THE  ACTION  OF  GLOBULINS  ON  THE  RESPIRATIONS. 

The  Action  of  Venom  Globulins  upon  the  Respiration  in  Normal  Animals. — 
Seven  experiments  were  made  with  globulins  upon  normal  animals :  three  with  the 
water-venom-ylobulin  of  the  Crotalus  adamanteus ;  and  one  with  the  u-akr-venom- 
glolmlin  of  Cobra;  one  with  the  copper-venom-globulin,  and  one  with  dialysis-venom- 
globulin,  both  from  the  Crotalns  adamanteus. 

These  poisons,  excepting  the  copper-venom-globulin,  all  act  like  the  pure  venoms, 
but  generally  with  a  less  degree  of  intensity,  causing  a  primary  acceleration  of  the 
respiration  followed  by  a  decline.  In  the  second  experiment,  however,  there  was 
no  diminution,  but  the  respirations  became  enormously  increased  so  that  at  death 
they  were  nearly  trebled  in  frequency.  The  copper-venom-globul'm  does  not  cause 
any  primary  acceleration,  but  simply  a  diminution. 


Experiment  No.  16. 


Normal 


Time: 
min.   sec. 

Respirations 
per  minute. 
100 

Length  of 
curve 
m.  m. 
9 

20 

100 

15 

40 

100 

12 

1 

00 

96 

11 

3 

00 

96 

9 

4 

00 

120 

10 

5 

00 

120 

10 

6 

00 

132 

10 

8 

00 

100 

10 

10 

00 

90 

9 

12 

00 

80 

9 

14 

00 

C9 

7 

14 

05 

.    .    . 

.    .    . 

14 

20 

80 

15 

14 

40 

60 

10 

16 

18 

,40 

40 

90 
96 

10 
-8 

20 

40 

108 

9 

22 

40 

114 

9 

24 

40 

108 

9 

26 

40 

90 

6 

28 

40 

96 

8 

30 

40 

72 

7 

32 

40 

64 

8 

34 

40 

70 

8 

36 

40 

75 

8 

38 

40 

80 

9 

40 

40 

90 

10 

44 

00 

*  •  • 

... 

REMARKS. 


Injected  intravenously  the  water-vertom-globulin  from 
0.015  gram  dried  venom  of  the  Crotalus  adamanteus. 


Injected  as  above  from  0.06  gram  dried  venom. 
Struggles. 


Dead.     Heart  arrested  in  diastole  ;  some  eochymoses. 


126 


THE    VENOMS   OF    CERTAIN   TH  A  N  A  TO  P  HID  E 


Experiment,  No.  17. 


Length  of 

Time: 

Respirations 

curve                                                   REMARKS. 

min.  sec. 

per  minute. 

m.  m. 

Normal      .  .  . 

75 

8        Injected  intravenously  0.0158  gram  water  '-venom-glob  >u- 

lin  (5  days  old)  from  the  dried  venom  of  Crotalus 

adamanieus. 

15 

80 

8         Struggles. 

30 

60 

.  .  . 

1     00 

60 

... 

1     30 

90 

... 

6     30 

110 

... 

11     30 

110 

.  .  . 

16     30 

110 

Injected  the  same  as  above. 

17     00 

120 

.  .  . 

27     00 

190 

... 

29     00 

Dead.     Blood  remains  fluid  ;  some  ecchymoses. 

Experiment  No. 

18. 

Time: 

Respirations 

REMARKS. 

min.  sec. 

per  minute. 

Normal     .  .  . 

114 

Injected  intravenously  the  water-venom-globulin  from  0.035  grain 

15 

.    .    . 

of  dried  Cobra  venom  dissolved  in  1  c.  c.  distilled  water. 

25 

126 

45 

132 

1     15 

150 

2     00 

150 

6     00 

204 

11     00 

114 

1C     00 

84 

26     00 

62 

33     00 

60 

56     00 

63 

66     00 

62 

76     00 

72 

120 

Killed.     Animal  in  fair  condition. 

Experiment  No. 

19. 

Time: 

Respirations 

REMARKS. 

min.  sec. 

per  minute. 

Normal      .  .   . 

73 

Injected  intravenously  the  water-venom-globulin  from  0.015  gram 

20 

84 

dried  venom  of  the  Crotalus  adamanteus. 

30 

78 

1     30 

120 

2     30 

108 

5     30 

96 

10     30 

96 

14     30 

82 

Haematuria. 

19     30 

70 

24     30 

75 

29     30 

78 

34     30 

72 

42     30 

69 

47     30 

72 

52     30 

96 

THE  ACTION  OF  VENOMS  UPON  RESPIRATION. 


127 


Time  : 

Respirations 

REMARKS. 

min.   sec. 

per  minute. 

57     30 

90 

67     30 

84 

77     30 

84 

80     30 

12 

85 

Dead.     Ecchymoscs  generally  ;  blood  fluid. 

Experiment  No. 

20. 

Length  of 

Time  : 

Respirations 

curve                                                     REMARKS. 

min.  sec. 

per  minute. 

m.  in. 

Normal      .   .   . 

180 

20        Injected  intravenously  the  copper-venom-globulin  from 

20 

174 

19            0.015  grain  dried  venom  of  the  Crotalus  adamanleus. 

40 

168 

19 

1     00 

168 

19 

3     30 

168 

20 

5     30 

108 

15 

7     30 

100 

9 

9     30 

110 

10 

11     00 

168 

17 

13     00 

138 

11 

15     00 

120 

10 

17     00 

144 

10 

19     00 

102 

9 

21     00 

108 

10 

23     00 

104 

7 

25     00 

112 

9 

27     00 

100 

9 

30     00 

90 

7 

34     00 

90 

7 

39     00 

112 

10 

41     00 

85 

8 

43     00 

96 

7 

45     00 

108 

5 

47     00 

108 

7 

49     00 

76 

6 

51     00 

66 

7 

53     00 

80 

8 

57     00 

96 

8 

59     00 

90 

9 

60     00 

116 

10 

63     00 

118 

8 

.    65     00 

116 

10         Struggles. 

69     00 

104 

9 

71     00 

100 

7 

73     00 

116 

7 

75     00 

100 

8 

77     00 

116 

11 

79     00 

140 

11 

81     00 

130 

10 

85     00 

130 

10 

87     00 

120 

10 

91     00 

126 

9 

92     00 

.  .  . 

...         Killed  by  pithing.    Lungs  very  much  ecchymosed  ;  abdo- 

minal  viscera  normal ;  heart  normal ;  blood  coagulates. 


128 


THE    VENOMS   OF    CERTAIN    T  II  A  N  A  T  0  P 11 1  D  E  M. 


Experiment  No.  21. 


Time  : 
miu.   sec. 

Normal      .   .   . 

Respirations 
per  minute. 

54 

Length  of 
curve 
m.  m. 

18 

10 

60 

16 

26 

54 

15 

40 

54 

15 

1     00 

48 

16 

3     00 

60 

17-42 

5     00 

72 

33 

7     00 

54 

30 

8     00  ^ 

63' 

32 

10     00  * 

60 

28 

11     30 

60 

30 

13     30 

72 

42 

15     30 

70 

38 

17     00 

78 

45 

17     10 

78 

42 

17     20 

102 

38 

18     20 

72 

38-78 

19     20 

66 

22 

21     20 

60 

23 

24     20 

70 

25 

27     20 

60 

29 

27     40 

60 

26 

28     20 

60 

25 

29     50 

Experiment  No. 

Time: 
min.   sec. 

Normal      .  .  . 

22. 

Respirations 
per  minute. 

112 

Length  of 
curve 
m.  m. 

9 

10 

120 

12 

20 

160 

16 

30' 

140 

16 

40 

140 

15 

1     00 

140 

16 

2     00 

126 

10 

5     00 

156 

14 

10     00 

174 

15 

12     00 

130 

14 

13     30 

142 

10 

13     50 

150 

22 

14     30 

132 

13 

19     00 

130 

9 

•    24     00 

120 

8 

29     00 

110 

10 

39     00 

80 

6 

54     00 

80 

3 

REMARKS 

Injected  intravenously  0.0012  gram  water-venom- 
globulin  from  the  dried  venom  of  the  Crotalus  ada- 
manteus. 


Struggles. 


Injected  0.0022  gram  tvater-venom-globulin. 


Struggles. 


Injected  0.0024  gram  water-venom-globulin. 


Killed  by  pitling  ;  some  ecchymoses. 


REMARKS 

Injected  intravenously  the  dialyxis-venom-globiilin  from 
0.015  gram  dried  venom  of  the  Crolalus  adamanleus. 


Injected   diafysis-venom-globulin  from   0.06  gram  of 
dried  venom. 


55     00 


Dead.  Respiration  ceased  before  the  heart.  Ecchy- 
moses in  the  lungs  and  in  the  pericardium,  in  the 
small  intestine,  ureters,  and  bladder. 


THE  ACTION  OF  VENOMS  UPON  RESPIRATION. 


129 


The  Action  of  Venom  Globulins  on  the  Respiration  of  Animals  in  whiclv  the 
Pueumogast ric  Nerves  were  Cut. — Two  experiments  were  made  on  animals  with 
cut  pneumogastric  nerves :  one  with  the  dialysis-venom-globulin,  and  one  with  the 
copper-venom-ylobulin,  both  from  the  Crotalus  adamanteus. 

In  neither  experiment  was  there  an  increase  in  the  respirations ;  these  results 
being  in  accord  with  the  experiments  made  with  pure  venom. 


Experiment  No.  23. 


Length  of 

Time: 

Respirations 

curve 

in  ill.     6CC. 

per  minute. 

in.  in. 

Normal      .  .  . 

42 

8 

10 

39 

10 

20 

30 

12 

40 

24 

8 

1     00 

27 

10 

1     20 

? 

... 

3     20 

20 

9 

5     20 

35 

8 

8     20 

24 

5 

18     20 

30 

5 

23     20 

32 

6 

36     20 

42 

7 

36     40 

42 

7 

38     40 

24 

20 

42     00 

Experiment  No. 

24. 

Length  of 

Time  : 

Respirations 

curve 

mill.  sec. 

per  minute. 

m.  m. 

Normal      .  .  . 

60 

5 

30 

54 

6 

1     00 

48 

5 

3     00 

48 

5 

8     00 

48 

5 

13     00 

52 

6 

15     00 

48 

6 

15     30 

30 

4 

15     40 

54 

15 

16     00 

?.. 

.  .  . 

16     30 

18 

10 

19     00 

12 

4 

24     00 

20 

4 

27     00 

20 

5 

30     00 

30 

5 

35     00 

26 

5 

39     00 

27 

5 

41     00 

30 

5 

44     00 

42 

6 

49     00 

30 

6 

REMARKS. 

Pneumogastric  nerves  previously  cut.  Injected  hypo- 
dennically  the  dialysis-venom-gJobulin  from  0.015 
grain  dried  venom  of  the  Crotalus  adamanteus. 


Struggles. 


Injected  dialysis-venom-globulin  from  0.06  gram/ 

Struggles. 

Respiration  ceased ;  heart  beats  feebly ;  blood  remains 
incoagulable;  great  ecchymoses  in  abdominal  viscera. 


REMARKS. 

Pneumogastric  nerves  previously  cut.  Injected  intra- 
venously the  copper-venom-globulin  from  0.015  gram 
dried  venom  of  the  Crotalus  adamanteus. 


Injected  copper-venom-globulin  from  0.03  gram  dried 
venom  in  two  doses. 

j  Struggles  with  very  irregular  breathing  followed  by 
|      gasping  respiration,. 


54     00 

17      June,  1886. 


Injected  copper-venom-globulin  from  0.12  gram  dried 

venom  in  two  doses. 
Respiration  ceased  ;  heart  still  beats ;  ecchymoses  in 

heart  and  lungs  marked. 


130 


THE    VENOMS   OF    CERTAIN   THANATOPIIIDE^E. 


The  results  of  these  experiments  with  the  globulins  indicate  that  the  water- 
venom-globuUn  and  dialysis-venom-ylobulin  act  like  the  pure  venom,  while  the 
copper-venom-glolulin  lacks  the  property  of  producing  the  primary  acceleration  of 
the  respirations. 


SECTION  III. — THE  ACTION  OF  VENOM  PEPTONES  ON  THE  RESPIRATION. 

The  Action  of  Venom  Peptones  on  the  Respiration  in  Normal  Animals. — Three 
experiments  were  made  on  the  normal  animals  with  the  venom  peptones ;  in  two 
with  the  peptone  from  the  Crotalus  adamanteus,  and  in  one  with  the  peptone  from 
the  Ancistrodon  piscicorus.  In  all  of  these  experiments  the  increase  of  the  respi- 
ration rate  was  strongly  marked. 


Experiment  No.  25. 


Normal 


Time: 
min.   sec. 

Respirations 
per  minute. 
225 

Length  of 
curve 
m.  m. 

G8 

10 

255 

60 

30 

255 

60 

1      00 

300 

56 

2     00 

270 

50 

5     00 

270 

50 

9     00 

270 

55 

Experiment  No.  26. 


Normal 


Time: 
min.  sec. 

Respirations 
per  minute. 

180 

Length  of 
curve 
m.  m. 
11 

10 

240 

16 

30 

270. 

15 

40 

240 

•    •    • 

] 

00 

345 

•    •    • 

1 

10 

270 

•    •    • 

1 

20 

240 

... 

4 

20 

240 

•    •    • 

9 

20 

300 

... 

18 

20 

360 

14 

28 

20 

270 

•    •   • 

33 

20 

ISO 

11 

REMARKS. 

Injected  intravenously  the  peptone  from  0.03  gram 
dried  venom  of  the  Crotalus  adamanteus  obtained 
by  boiling. 


Killed.     Blood  clots  readily;  moderate  ecchymoscs  in 
the  lungs 


REMARKS. 

Injected  intravenously  the  peptone  from  O.Ofi  gram 
dried  venom  of  the  Ancistrodon  piscicorus  obtained 
by  boiling. 


THE  ACTION  OF  VENOMS  UPON  RESPIRATION. 


131 


Experiment  No.  27. 


Normal 


Length  of 

Time  : 

Respirations 

curve 

min. 

sec. 

per  minute. 

in.  in. 

. 

.    . 

75 

9 

10 

120 

42 

3 

00 

30 

10 

6 

00 

75 

8 

11 

00 

50 

8 

18 

00 

48 

7 

23 

00 

50 

7 

28 

00 

45 

7 

33 

00 

60 

7 

37 

00 

60 

9 

49 

... 

.    .    . 

REMARKS. 

Injected  intravenously  the  peptone  from  0.015  gram 
dried  venom  of  the  Crotalus  adamanteus. 


Dead.     No  ecchymoses;  lungs  slightly  congested. 

In  one  animal  the  increase  was  equal  to  one-third  of  the  normal ;  in  the  second, 
in  which  a  larger  dose  was  used,  the  normal  rate  was  doubled;  and  in  the  third 
it  rose  to  more  than  one-half  of  the  normal.  There  was  not,  however,  in  any  of 
the  animals  that  marked  depression  which  is  observed  in  poisoning  with  pure 
venom  or  venom  globulins. 

The  Action  of  Venom  Peptones  on  the  Respiration  in  Animals  in  which  the 
Pneumogastric  Nerves  had  been  previously  Divided. — In  one  experiment  in  which 
the  pneumogastric  nerves  were  cut  and  in  which  the  peptone  from  the  venom  of 
the  Crotalus  adamanteus  was  used,  the  well-marked  primary  increase  in  the  respi- 
rations did  not  occur,  there  being  a  diminution  from  the  first. 


Experiment  No.  28. 


Normal 


Time  : 
min.  sec. 

Respirations 
per  minute. 
80 

Length  of 
curve 
m.  m. 
13 

10 

52 

18 

15 

37 

12 

20 

25 

8 

30 

22 

7 

1 

00 

30 

8 

1 

30 

30 

7 

3 

30 

40 

9 

8 

30 

60 

8 

15 

30 

36 

13 

20 

30 

48 

17 

25 

30 

50 

14 

30 

30 

52 

15 

35 

00 

55 

12 

40 

00 

48 

15 

45 

00 

45 

15 

50 

00 

45 

16 

62 

00 

44 

15 

REMARKS. 

Injected  intravenously  the  peptone  from  0.015  gram 
.  dried  venom  of  the  Crotalus  adamanteus. 


Struggles. 


Killed  by  pithing. 

In  this  experiment,  as  in  those  with  pure  venom  and  venom  globulins  in  which 
the  animals  had  the  pneumogastrics  cut,  the  increased  respiration  rate  seen  in 
normal  animals  did  not  occur. 


132  THE   VENOMS   OF    CERTAIN   TH  AN  A  T  0  P  HID  E 

The  results  of  the  experiments  with  venom  peptone  are  therefore  in  accord  with 
those  with  the  pure  venom  and  the  venom  globulins. 

Summary. — From  the  results  of  the  observations  with  pure  venoms  and  their 
globulins  and  peptones  upon  the  respiration  it  seems  clear  that  the  primary  action 
of  all  of  the  above  poisons,  excepting  the  copper-venom-globulin,  is  to  cause  an 
increase  in  the  number  of  respirations,  and  secondarily  to  diminish  the  respirations 
below  the  normal.  Of  the  different  principles  the  peptone  seems  to  exert  the  most 
decided  power  in  causing  the  acceleration,  while  the  copper-venom-globulin  seems 
to  utterly  lack  this  action. 

Since  the  primary  increase  of  the  respirations  does  not  occur  in  any  case  after 
section  of  the  pneumogastric  nerves,  this  effect  must  be  exerted  by  an  action  of  the 
poisons  upon  the  peripheries  of  these  nerves,  and  since  after  section  of  these  nerves 
a  diminution  of  the  respirations  always  occurs  this  effect  must  be  due  to  a  depres- 
sion of  the  respiratory  centres,  as  we  have  found  that  the  motor  nerves  and  muscles 
of  respiration  are  irritable  long  after  the  cessation  of  this  function. 


PATHOLOGY.  133 


CHAPTER    X. 

PATHOLOGY. 

Pathology  of  Serpent  Venoms. — The  pathology  of  snake  poisoning  in  man  owes 
most  of  what  is  best  in  our  knowledge  of  it  to  the  researches  of  the  East  Indian 
surgeons  and  to  American  observers. 

In  the  following  observations  Prof.  H.  F.  Formad  has  followed  with  great  suc- 
cess the  lines  of  a  research  which  were  laid  down  with  care  by  the  authors  of  this 
essay.  They  have  also  been  at  great  pains  to  repeat,  and  to  verify,  most  of  the 
observations  made  by  this  distinguished  observer. 

The  Nature  and  Character  of  the  Individual  Morphological  Constituents  of 
Venom. — Having  seen  that  fresh  venom  consists  morphologically  of  a  liquid  and 
of  a  solid  part,  it  was  necessary  to  ascertain  the  exact  nature  and  character  of 
each. 

The. following  means  were  resorted  to: — 

1st.  The  separation  of  the  granular  material  (of  fresh  venom)  by  filtration  and 
the  submission  to  physiological  tests  of  the  liquid  filtrate  and  of  the  solid  residue, 
each  separately. 

2d.  The  exposure  of  fresh  venom  to  a  temperature  high  enough  to  kill  organized 
life,  and  then  submitting  it  to  physiological  tests. 

3d.  Studying  the  effects  of  venom  and  of  its  isolated  morphological  constituents 
upon  dead  animal  Substances.  (Putrefaction  and  other  experiments.) 

4th.  The  isolation  and  culture  of  the  organisms  contained  in  venom  and  the 
testing  of  the  physiological  effects  of  these  isolated  and  washgd  organisms  (viz.,  of 
pure  cultures  of  micrococci). 

1st.  Filtration  Experiments  with  Fresh  Venom. — On  account  of  its  viscid  and 
glutinous  character  venom  could  not  be  satisfactorily  filtered  except  under  a  high 
pressure  through  a  vacuum  filter.  About  two  drachms  of  fresh  Crotalns  adamanteus 
venom  were  forced  by  means  of  a  hydraulic  air  pump  through  a  porous  clay  cylin- 
der such  as  is  employed  in  certain  small  galvanic  batteries,  or  else  the  venom 
was  filtered  through  a  thin  layer  of  plaster  of  Paris  moulded  in  the  neck  of  a 
small  glass  filter.  The  liquid  filtrate  obtained  was  perfectly  clear,  and  examined 
under  the  microscope  showed  no  organic  or  solid  particles  of  any  kind.  The  solid 
residue  left  upon  the  filter  consisted  of  granular  material,  such  as  has  been  described 
before,  of  bacteria  and  a  few  cells.  This  residue  was  diligently  and  repeatedly 
washed  with  boiled  distilled  water,  by  passing  the  latter  through  the  filter. 

The  amount  of  residue  (about  three  grains)  just  obtained  was  dried  and  intro- 
duced subcutaneously  into  the  pectoral  muscle  of  a  pigeon,  but  without  effect. 


134  THE    VENOMS    OF    CERTAIN    THANATOPHIDE^E. 

Two  pigeons  were  injected  in  the  pectoral  muscle,  one  with  five,  and  the  other 
with  two  minims  of  the  liquid  filtrate  above  described,  and  both  died  promptly 
within  six  minutes  and  twenty-five  minutes  respectively. 

2d.  Experiments  icith  Heated  Vcnom.-^ Fresh  Crotalus  venom  rapidly  dried  was 
put  in  a  covered  watch-glass  and  subjected  for  one  hour  to  a  temperature  of  115°  C. 
in  the  dry-heat  oven.  The  venom  was  thereby  converted  into  a  dense  resinous 
opaque  brown  mass. 

Two  grains  of  this  mass,  upon  the  addition  of  distilled  water  forming  a  turbid 
liquid,  were  divided  into  thirds  and  injected  hypodermatically  into  a  rabbit,  a  rat, 
and  a  pigeon,  respectively.  The  rabbit  died  in  15  minutes,  the  rat  in  12  minutes, 
and  the  pigeon  in  7  minutes,  after  the  operation,  with  results  and  lesion  similar  to 
those  obtained  by  the  use  of  fresh  venom. 

This  experiment  also  shows  that  the  virulence  of  venom  does  not  reside  in  any 
of  its  organized  constituents. 

3d.  Putrefaction  Experiments. — The  testing  of  the  effects  of  venom  on  various 
dead  animal  substances  was  particularly  desirable  on  account  of  the  remarkable 
capacity  of  the  venom  to  induce  rapid  putrefaction  in  the  tissues  of  living  animals. 
It  was  necessary  to  learn  whether  this  property  of  bringing  about  speedy  necrotic 
changes  was  an  action  inherent  in  venom  or  due  to  any  of  its  accidental  constituents. 

Putrefaction  Experiments  iritk  Sterilized  Bouillon  and  Fresh  Venom  and  its  Active 
Principles  (not  Sterilized}. — This  bouillon  was  prepared  from  chicken  in  the  same 
manner  as  that  ordinarily  used  for  culture  liquids  for  bacteria,  and  the  experiments 
were  executed  in  a  room  at  a  temperature  of  about  70°  F. 

About  two  drachms  of  sterilized  bouillon  were  put  in  each  of  sixteen  ordinary 
test  tubes  which  were  then  treated  as  follows  : — 

Tubes  1  and  2,  added  to  bouillon  one  drop  of  fresh  Crotalus  venom ;  mouth  of 
tubes  plugged  with  cotton. 

Tubes  3  and  4,  prepared  same  as  last,  but  tube  left  open  (no  cotton  plug). 

Tubes  5  and  6,  added  one  grain  of  Crotalus  peptone.  Tube  closed  by  cotton 
plug. 

Tubes  7  and  8,  same  as  last,  but  tubes  left  open. 

Tubes  9  and  1 0,  added  one  grain  of  Crotalus  globulin.     Tubes  closed. 

Tubes  11  and  12,  same  as  last.     Tubes  open. 

Tubes  13  and  14,  a  pure  bouillon,  nothing  added  to  it.     Tubes  closed. 

Tubes  15  and  16,  same  as  last.     Tubes  open. 

Twenty-four  hours  later  the  bouillon  in  all  the  test  tubes  which  originally  was 
perfectly  clear  had  become  cloudy  except  tubes  13  and  14  (which  contained  the 
sterilized  pure  bouillon  plugged  well  with  cotton). 

On  the  third  day  of  the  experiment  tubes  3  and  4  (fresh  venom,  tubes  open) 
showed  well-pronounced  putrefaction  of  the  bouillon. 

Slight  putrefactive  changes  were  subsequently  observed  in  the  remaining  tubes 
(except  13  and  14)  in  the  following  order : — 

On  the  fourth  day,  tubes  7  and  8.  On  the  fifth  day,  tubes  11  and  12,  also  in 
tubes  15  and  16. 

On  the  seventh  day  all  the  plugged  specimens  were  examined,  and  all  showed 


PATHOLOGY.  135 

more  or  less  putrescence  except  the  tubes  with  the  pure  bouillon  as  stated.  Of 
those  closed  test  tubes,  however,  tubes  1  and  2  (the  fresh  venom)  showed  the 
putrefactive  changes  to  be  much  more  pronounced  than  in  the  remaining  tubes  ; 
but  as  we  have  seen  putrefaction  ensued  much  sooner  in  the  tubes  that  were  open 
(tubes  3  and  4). 

As  all  the  tubes  showed  putrefaction  more  or  less,  it  is  presumable  that  the 
peptone  and  globulin  accidentally  contained  bacteria,  these  substances  not  having 
been  sterilized  at  the  commencement  of  the  experiment. 

The  contents  of  the  tubes  examined  microscopically  during  and  at  the  end  of  the 
experiment  showed  the  presence  of  bacteria  of  putrefaction  in  direct  proportion  to 
the  putrefaction  changes. 

Imperfect  as  this  experiment  may  be,  it  appears  to  establish  the  fact  that  fresh 
venom  promotes  putrefactive  changes  comparatively  more  rapidly  than  the  venom 
peptone  and  globulin,  but  it  also  shows  further  that  this  power  to  produce  putres- 
cence is  very  much  aided  by  the  action  of  the  air,  and  depends  upon  the  presence 
of  bacteria  contained  in  that  air  or  in  the  venom.  It  was  also  evident  that  putre- 
faction was  considerably  retarded  in  all  the  tubes  that  were  plugged  by  the  cotton, 
and  further  that  unplugged  tubes  containing  sterilized  soup,  and  exposed  to  contami- 
nation from  air  showed  also  putrefaction  but  at  a  later  date. 

Putrefaction  Experiment  with  Muscular  Tissue  and  Venom. — The  following  rough 
experiment  also  appears  to  show  that  putrefactive  changes  develop  in  dead  animal 
tissues  much  more  rapidly  in  the  presence  of  venom  than  without  it. 

Experiment. — A  few  drops  of  a  solution  of  dry  Crotalus  venom  were  poured  upon 
a  small  piece  of  fresh  muscle  just  removed  from  the  thigh  of  a  rabbit  and  placed 
in  a  covered  glass  beaker. 

A  similar  preparation  but  without  the  addition  of  venom  was  made  in  a  second 
covered  beaker.  Temp.  70°  to  80°  F. 

Putrefactive  changes  began  to  appear  in  the  specimen  treated  by  the  venom  after 
twenty-four  hours,  and  after  seventy-two  hours  were  quite  far  advanced.  Under 
the  microscope  the  muscular  tissue  showed  necrotic  alterations  very  similar  to 
those  (to  be  described  later)  as  occurring  in  experiments  upon  the  living  muscle. 
A  multitude  of  dumb-bell-shaped  rod  bacteria,  some  large  bacilli  and  the  micrococci 
of  the  venom  enormously  multiplied,  were  seen  in  the  decaying  muscular  substance. 

In  the  specimen  of  muscle  not  treated  by  venom,  putrefactive  changes  were 
delayed  to  the  fifth  day  and  then  appeared  to  be  much  less  conspicuous,  showing 
but  few  bacteria.  The  muscle  fibres  were  uniformly  cloudy  and  degenerated  but 
not  broken  down  in  the  peculiar  manner  caused  by  venom. 

Experiments  with  Bouillon  and  Venom  in  Sealed  Glass  Bulbs,  Venom  being 
thoroughly  Sterilized. — More  satisfactory  and  conclusive  results  were  obtained  from 
the  following  experiments:  — 

A  number  of  small  glass  bulbs  were  filled  with  sterilized  bouillon  after  the  well- 
known  method  of  Dr.  Sternberg,  and  after  being  thoroughly  resterilized  by  boiling 
the  following  preparations  were  made : — 

To  each  of  six  bulbs  was  added  one  grain  of  dry  Crotalus  venom,  the  venom 
having  been  previously  subjected  to  sterilization  in  a  dry  heat  at  110°  C.  for  one 


136  THE   VENOMS    OF   CERTAIN   THANATOPHIDE^B. 

hour.  The  bulbs  were  'then  hermetically  sealed  by  melted  glass.  The  bouillon  in 
these  tubes  (with  sterilized  venom)  remained  perfectly  clear  and  free  from  bacteria. 
Microscopical  examination  was  made  at  various  periods,  the  last  time  after  eighteen 
months  when  it  was  still  perfectly  clear  and  showed  no  signs  of  putrefaction. 

A  similar  result  was  obtained  in  an  experiment  with  another  set  of  six  glass 
bulbs  tilled  with  bouillon,  and  to  which  some  Moccasin  peptone,  previously  sterilized, 
was  added.  These  bulbs  looked  somewhat  cloudy,  but  on  examination  of  the  con- 
tents eighteen  months  later  no  bacteria,  and  no  putrefactive  changes  were  noted. 

As  a  control  experiment  six  bulbs  filled  with  pure  sterilized  bouillon  were  kept 
for  a  similarly  long  period,  and  they  all  remained  clear  and  free  from  change;  while 
a  few  bulbs  filled  with  unsterilized  bouillon  showed  great  cloudiness,  bacteria,  and 
putrefactive  change. 

4th.  Culture  Experiments. — The  study  of  the  morphology  of  the  bacteria  inhabit- 
ing the  venom  was  next  undertaken.  To  this  end  numerous  culture  experiments 
to  isolate  the  bacteria  from  the  venpm  were  made.  As  stated  before,  the  perfectly 
fresh  venom  contained  only  one  form  of  these  vegetable  organisms,  the  micrococci, 
and  only  to  these  latter  attention  was  paid ;  the  rod  bacteria  and  bacilli  not 
appearing  except  in  venom  which  had  began  to  putrefy. 

The  micrococci  contained  in  the  venom  showed  the  following  behavior  in  pure 
cultures :  Of  culture  soils,  the  peptonized  gelatine  prepared  after  the  formula  of 
Koch  proved  to  be  quite  suitable.  The  isolation  of  the  micrococci  was  made  after 
the  methods  of  Sternberg  and  of  Koch,  as  adopted  in  the  pathological  laboratory  of 
the  University  of  Pennsylvania.  For  gelatine  culture  a  minute  quantity  of  venom 
was  smeared  on  the  surface  of  the  solidified  jelly  contained  in  a  sterilized,  small, 
flat,  well  covered  glass  vessel.  The  micrococci  liquefied  the  jelly,  an  effect  not 
peculiar  to  all  bacteria.  After  twenty-four  hours  all  over  the  inoculated  surface 
of  the  jelly  were  seen  small  turbid  drops  which  contained  the  micrococci.  With  a 
sterilized  platinum  wire  the  micrococci  from  one  of  the  liquefying  specks  upon  the 
first  culture  were  transplanted  to  the  jelly  in  a  second  culture  vessel.  From  this 
second  generation  a  minute  quantity  was  transplanted  to  a  third  and  fourth  culture 
vessel.  The  fourth  and  all  the  later  generations  yielded  usually  a  pure  crop  of 
micrococci. 

In  impure  cultures  dumb-bell-shaped  bacteria  and  sometimes  large  bacilli  were  met 
with.  These,  however,  could  not  be  said  to  be  peculiar  to  venom,  as  they  are  never 
found  in  fresh  venom.  It  may,  therefore,  be  concluded  that  these  cultures  represent 
the  micrococci  peculiar  to,  or  at  least  those  constantly  inhabiting  venom.  More- 
over, the  micrococci  in  these  cultures  whenever  they  were  successful,  were  the 
only  bacterium  seen  and  were  fully  identical  as  to  shape,  measurement,  and  be- 
havior to  aniline  dyes  with  those  found  in  the  fresh  venom. 

Much  better  crops  of  the  venom-micrococci  were  obtained  in  bouillon  cultures  in 
Sternberg's  glass-bulbs.  The  micrococci  grow  more  rapidly  and  better  in  these 
bulbs,  because  the  bouillon  can  be  heated  up  to  the  more  suitable  temperature  of 
40°  C. ;  while  the  jelly  cultures  could  not  be  warmed  to  such  a  degree  without  melt- 
ing solid  gelatine.  A  variety  of  other  culture  soils  and  methods  of  isolation  were 


PATHOLOGY.  137 

employed  in  these  experiments,  but  their  description  here  is  unnecessary  as  not 
being  sufficiently  related  to  the  points  at  issue. 

In  relation  to  the  morphology  of  the  micrococci  it  may  be  added,  that  they 
measure  on  the  average  ?oii7zr  °f  an  mcu  m  diameter;  they  often  appear  in  pairs, 
but  most  commonly  in  zooglcea  masses.  They  show  a  distinct  aureole,  such  as  is 
met  with  in  various  forms  of  micrococci.1 

These  aureoles  have  lately  been  erroneously  described  by  Friedlander,  as  peculiar 
to  certain  "  specific"  micrococci  in  croupous  pneumonia.  In  conclusion,  it  might 
be  said  that  the  venom  micrococci  do  not  appear  to  differ  from  the  micrococci  found 
in  the  saliva  of  men  and  other  animals. 

In  order  to  test  whether  the  venom-micrococci  were  in  any  way  specific  or  patho- 
genetic,  and  whether  they  form,  or  contribute  to,  the  virulence  of  the  venom,  inocu- 
lations with  pure  cultures  of  the  micrococci  were  made  upon  animals. 

As  these  experiments  gave  entirely  negative  results,  it  is  superfluous  to  enter 
into  details.  Suffice  it  to  say  that  large  quantities  of  the  pure  micrococci  from  a 
sixth  generation  were  injected,  in  various  manners,  into  rabbits,  cats,  pigeons,  and 
white  rats,  but  without  fatal  results ;  or  without  producing  any  other  lesion  than 
occasionally  local  abscesses,  or  later  on,  metastatic  abscesses.  Sometimes  the  so- 
called  "miliary  tuberculosis  of  animals"  was  produced  by  inoculating  with  the 
venom-micrococci.  No  signs  of  any  lesions  resembling  those  of  venom  poisoning 
were  observed. 

Experiments  made  to  Study  tlie  Anatomical  Changes  produced  by  the  Venom  in  liv- 
in,ij  Animals.  Nah-fd  V.ye  Appearances. — Very  many  years  ago  Dr.  Weir  Mitchell 
described  two  forms  of  venom  poisoning — rapid  or  acute,  and  slow  or  chronic.  To 
the  latter  appear  to  be  relegated  by  him  all  those  cases  in  which  death  is  protracted 
beyond  a  few  hours.  This  convenient  division  is  justified  by  certain  differences 
in  the  mode  of  termination  of  venom  poisoning,  and  by  the  macroscopic  and  micro- 
scopic appearances  of  the  lesions  induced. 

In  the  most  rapid  poisoning,  there  is  frequently  nothing  appreciable  to  the  naked 
eye  beyond  the  slight  local  lesion  or  here  and  there  minute  capillary  hemorrhages, 
when  death  has  been  delayed  beyond  a  minute.  In  examples  of  chronic  poisoning 
both  the  local  and  the  systemic  changes  are  enormously  more  extensive.  When 
animals  were  subjected  to  chronic  poisoning  they  were  kept  under  the  influence  of 
narcotics,  since  it  had  been  learned  that  these  agents  did  not  affect  the  results. 
No  Cobra  venom  was  employed  in  this  series,  but  only  the  pure  or  dried  venoms 
of  our  own  serpents,  or  else  some  one  or  other  of  the  constituents  of  these  poisons. 

The  following  tables  relate  the  experiments  made,  and  the  more  striking  mor- 
phological changes: — 

1  See  "Memoir  on  Diphtheria,"  Report  to  the  National  Board  of  Health,  1882,  by  H.  C.  Wood 
and  H.  F.  Forrnad. 


18      June,  1886. 


138 


THE    VENOMS    OF    CERTAIN    T  II  A  N  A  T  0  P  H  1  D  E  M. 


RAPID  POISONING. 

Effects  of  Venom  when  Injected  Ili/poilermaticaVy  into  or  Applied  otherwise  to  the  Tissues 

of  the  Living  Animal. 


No.  of 
expt. 

Animal 
used. 

Form  and  quantity 
of  venom,  and 
where  introduced. 

Time  of 

death. 

Local  lesion. 

Condi- 
tion of 
blood. 

Changes  in  thorax,  abdomen, 
brain,  and  membranes. 

REMARKS. 

1 

Pigeon 

Crotalus  venom, 

Killed 

Moderately  sized, 

Coagu- 

All  internal  organs  congested  ; 

This    animal    was    killed 

fresh,  j  grain  in- 

after 5 

dark  hemorrha- 

lable 

no  other  changes  visible;  no 

before  the  full  effects   of 

jected  into  pecto- 

minutes 

gic  swelling 

and  red 

ecchymoses  perceptible 

the  venom. 

ral  muscle 

2 

Pigeon 

Same  as  last 

Died 

Very  dark  colored 

LrSS   DO- 

Organs  only  moderately  con- 

For the  details  and  the  his- 

in  15 

hemorrhagic 

agulabh- 

gested,   but  there  were   nu- 

tological appearances,  see 

minutes 

swelling 

and 

merous     small      snbpleural. 

the   next   chapter.     The 

quite 

subperitoneal,      and     slight 

studies    of    the    changes 

dark 

snbpericardial  ecchymoses 

in  muscular  tissue  were 

mostly    made    from    this 

experiment. 

3 

Pigeon 

Moccasin  venom, 

Died 

Profuse  hemor- 

Liquid 

Ecchymoses  in  nearly  all  or- 

fresh, 1  drop  in- 

after 1 

rhage  all  over 

very 

gans,  quite  marked  in  arach- 

jected into  peri- 

hour 

peritoneal 

dark 

noid  and  at  base  of  brain  ; 

toneum 

and  50 

cavity 

some  so  small  as  to   be  visi- 

minutes 

ble  only  by  microscope.    Ex- 

treme congestion 

4 

Pigeon 

Crotalus  venom, 

Died 

Same  as  last 

Liquid 

Hemorrhages   only   subperito- 

fresh,  1  drop  into 

in  25 

dark 

neal,    other    organs    merely 

peritoneum 

minutes 

congested 

5 

Rabbit 

Moccasin  venom, 

9 

Subperitoneal 

Coagu- 

No   changes   beyond    local 

injected  into  peri- 

minutes 

hemorrhages 

lable  on 

lesion 

toneum 

exposure 

6 

Pigeon 

Peptone,  injected 

35 

Hemorrhagic 

Liquid 

No  visible  changes,  except  all 

Changes  in  muscular  tis- 

into pectoral 

minutes 

swelling 

organs  congested 

sue  similar  to  those  pro- 

muscle 

duced    by   fresli    venom, 

but  far  less  blood  effused. 

7 

Pigeon 

Moccasin  venom, 

5 

Hemorrhages  in 

Slightly 

Membranes  of  brain  and  brain 

fresh,  injected 

minutes 

arachnoid  and 

coagu- 

substance  peripherally  soak- 

into cavity  of 

brain  tissue 

lable 

ed  with  blood  ;  other  organs 

skull 

congested 

8 

Rabbit 

Moccasin  venom, 

1 

Lung  infarcted 

Same  as 

No   changes,   except    in    lung 

See  specimen  and  descrip- 

fresh, ^  grain  in- 

minute 

by  blood 

last 

and  some  subpericardial  ec- 

tion in  chapter  on  histo- 

jected  into  lung 

chymoses 

logical  changes. 

9 

Rabbit 

Peptone,  ^  grain 

43 

Ecchymosis 

Liquid 

Other    organs    not    visibly 

into  liver  and 

minutes 

locally  only 

dark 

affected 

peritoneum 

10 

Rabbit 

Same  as  last 

Killed  at 

Slight  subperito- 

Dark, 

No  systemic  changes. 

the  end 

neal  ecchymoses 

but  co- 

of  1  hour 

agulable 

11 

Pigeon 

Peptone,  1  grain 

20 

Local  ecchymoses 

Ditto 

1 

rHistological    changes 

into  peritoneum 

minutes 

slight 

!  No  notable  changes  in  other 

I      similar  to  those  pro- 

12 

Pigeon 

Globulin,  £  grain 

40 

The  same  as  last 

Ditto 

organs 

duced     by    fresh 

into  peritoneum 

minutes 

j 

venom. 

13 

Cat 

Crotalus  globulin, 

40 

Profuse  ecchy- 

Slightly 

Hemorrhage  only  local 

*\ 

$  grain  into  peri- 

minutes 

mosis 

coagu- 

toneum 

lable 

14 

Catf 

Crotalus  peptone, 

1  hour 

Same  as  last,  but 

Liquid 

Hemorrhage   only   local,   also 

Microscopic  examination 

^  grain  into  peri- 

and 20 

less  marked 

extreme    congestion    of     all 

made  of   every  organ. 

toneum 

minutes 

organs 

The    details    will     be 

15 

Rabbit 

Crotalus  globulin, 

Killed 

Same  as  last 

Red  and 

Nothing    peculiar  beyond  the 

given  hereafter. 

^  grain  into  peri- 

in 10 

coagu- 

local  lesion 

toneum 

minutes 

lable 

16 

Rabbit 

Dry  Crotalus 

Killed 

Same  as  last 

Same  as 

Same  as  last 

venom,  ^  grain  in 

in  10 

last 

watery  solution, 

minutes 

into  peritoneum 

17 

Rabbit 

Dry  Crotalus  I 

Died 

Same  as  last 

Very 

Ecchymoses  in  all  organs  ex- 

Some  of    the   ecchymoses 

venom,  £  grain  in 

1  hour 

dark, 

amined.      Profuse  ecchymo- 

were so  small   as  to  be 

watery  solution, 

and  25 

liquid 

ses  in  peritoneum,  also  sub- 

visible    only    on    micro- 

into peritoneum 

minutes 

pleural,    subarachnoid,   and 

scopical  examination. 

subpericardial.  Liver,  which 

was  injured  by  the  syringe, 

showed  a  large  hemorrhagic 

infarction 

PATHOLOGY. 


139 


RAPID  POISONING  —CONTINUED. 


No.  of 
expt. 

Animal 
used. 

Form  and  quantity 
of  venom,  and 
where  introduced. 

Time  of 

death. 

Local  lesiou. 

Condi- 
tion of 
blood. 

Changes  in  tin  mix,  abdomen, 
brain,  and  membranes. 

REMARKS. 

18 

Cat 

Dry  Ootalus 

Died 

Same  as  last 

Same  as 

Peritoneal    cavity   contains    a 

Cats   appear  to  resist  the 

venom,  1  grain  in 

5^  hours 

last 

good  deal  of   liquid    blood  ; 

(•fleets    of    venom    much 

watery  solution, 

hemorrhage  at  base  of  brain 

longer    than    the    other 

into  peritoneal 

(subarachnoid)  ;      no    other 

animals  used  in  this  re- 

cavity 

lesion  noted  ;   organs  rather 

search. 

ana?mie.     Heart  empty,  con- 

tracted 

19 

Cat 

Peritoneum  opened, 

Died 

llrmorrhagic  in- 

Partly 

Peritoneal     hemorrhage  ;    or- 

It appears  that  when  the 

(chlor- 

mesentery  exposed 

after  4 

filtration,  quite 

coagu- 

gans  anii'iiiic 

mesentery  is  i:r/mxtil  and 

alized) 

uninjured,  in 

hours 

extensive,  but 

lable 

not   injured    the   animal 

moist  chamber, 

and  35 

came  on  very 

survives  much  larger  ap- 

and smeared  re- 

minutes 

slowly 

plications  of  venom  than 

peatedly  with  a 

if  venom  be  injected  into 

solution  of  dry 

an   unopened    peritoneal 

venom,  using  not 

cavity.  Very  small  quan- 

less than  5  grains 

tities  of  venom  appear  to 

of  venom 

kill   in   the   latter   case. 

For  further  experiments 

of    this    character,     see 

Mechanism    of     Hemor- 

rhages. 

None  of  the  cases  in  the  table  exhibit  instances  of  the  greatest  possible 
rapidity  of  death.  Dr.  Mitchell  has  seen  a  pigeon  die  within  ten  seconds  from  a 
hypodermatic  injection  of  pure  Crotalus  venom.  In  such  a  case  there  is  positively 
no  lesion,  and  the  blood  is  solidly  coagulated. 

In  most  cases  very  soon  after  injection  of  the  venom  in  either  of  its  forms,  the 
time  varying  from  a  few  minutes  to  a  few  hours,  according  to  the  kind  of  animal 
and  the  quantity  of  venom  used,  there  appears  a  swelling  at  the  point  of  injection 
with  intense  violet-black  discoloration  of  the  skin,  which  gradually  extends  over 
an  area  of  several  square  inches.  On  making  an  incision  into  the  tissues  in  the 
immediate  neighborhood  of  the  injection,  they  are  found  to  be  soaked  with 
extravasated  blood.  This  is  often  all  that  is  visible  if  death  has  occurred  soon; 
but  if  it  has  been  postponed  for  a  short  time,  then  in  tissues  distant  from  the  place 
of  the  injection,  extravasations  to  a  smaller  extent  were  often  found.  Most  pro- 
nounced and  most  frequent  are  the  ecchymoses  below  serous  membranes  (subpleural, 
subperitoneal,  and  subpericardial)  ;  in  fact  the  whole  organism  is  deeply  affected, 
the  tissues  being  congested  and  presenting  a  much  darker  appearance  than  normal. 
The  blood  does  not  seem  to  coagulate  readily  within  cavities  or  interstices  of  the 
body  unless  death  follmcs  almost  instantaneously.  In  cases  which  live  longer,  the 
blood  remains  commonly  in  a  liquid  state,  or  coagulates  imperfectly,  and  then  only 
after  being  exposed  to  the  air,  resembling  in  this  particular  the  state  of  that  fluid 
observed  in  conditions  of  asphyxia. 


140 


THE   VENOMS   OF   CERTAIN   THAN AT OPHITES. 


SLOW  POISONING. 
Effects  of  Venom  upon  the  Tissues  of  the  Living  Animal. 


No.  of 
expt. 

Animal 
used. 

Form  and  quantity 
of  venom,  and 
where  introduced. 

Time  of 
death. 

Local  lesion. 

Condi- 
tion of 
blood. 

Changes  in  internal  organs. 

REMARKS. 

20 

Pigeon 

Copper  globulin, 

13 

Large,  dark  gan- 

Liquid 

Subperieardial     ecchymoses     and 

2  c.  c.  (equal  to  1 

hours 

grene  like  swell- 

and 

pericardia!  effusion.     Red  tinged 

gram  fresh  venom) 

ing  of  chest  ; 

dark 

serum  in  peritoneal  cavity.  Heart 

injected  into  pec- 

muscle disinte- 

empty.     Lungs  and  pleura  full 

toral  muscle 

grated 

of  ecchymoses.      All  the  organs 

congested 

21 

Rabbit 

Unknown,  but  very 

9  days 

Dark  gangren- 

Liquid 

Numerous  minute  hemorrhages  be- 

All    these    autopsies 

minuLe  quantity 

ous  swelling 

and 

low  serous  membranes,  seen  also 

were   made    immedi- 

of Crotalus  venom 

dark 

at  base  of  brain  in  right  posterior 

ately  or  quite  shortly 

injected  in  back 

fossa.    The  organs  rather  anaemic 

after  death. 

and  softened 

22 

White 

Crotalus  venom, 

2  days 

Hemorrhagic 

Slightly 

Organs  congested,  softened  ;  noth- 

For changes  in  blood, 

rat 

dry,  £  grain  in- 

and 7 

peritonitis 

coagu- 

ing  else  peculiar  found  ;    small, 

see  details  in  text. 

jected  into  abdo- 

hours 

lable, 

loose,  red  clot   in  right   side  of 

men 

dark 

heart 

23 

Cat 

Crotalus  venom, 

9  days 

Skin  slough  over 

Liquid 

All  internal  organs  softened  and 

dry,  1  grain  in- 

and 2 

local  lesion, 

dark,  ill 

highly  ecchymosed  and  congested. 

jected  into  right 

hours 

which  is  dark, 

smelling 

Feces  and  urine  bloody.     Hemor- 

thigh 

hemorrhagic, 

rhage  at  base  of  brain,  and  min- 

• 

and  gangrenous 

ute  blood  specks  in  pericardium. 

Heart  quite  atrophied  and  softened 

24 

Pigeon 

Quantity  unknown, 

14  days 

Atrophy,  with 

Liquid 

Hemorrhages  indicated  by  deposits 

For  further  details 

injected  into  pec- 

pigmentation of 

and 

of  blood  pigment  in  the  tissues. 

of  the  histological 

toral  muscle 

the  pectoral 

very 

All  the  organs  in  a  state  of  atro- 

chances, see  text. 

muscle  injected 

dark 

phy    and    softened,    resembling 

acute  yellow   atrophy   in    man. 

N.  B.  —  Gangrenous 

Serous  sacks  all  distended  with 

changes  in  the  local 

bloody  serum.    Heart  empty,  and      lesion    are    usually 

although  contracted  quite  soft 

more  pronounced   in 

the  "Slow"  than  in 

the    Rapid    form    of 

venom  poisoning. 

The  following  lesions  may  be  mentioned  as  peculiar  to  retarded  or  slow  poison- 
ing: Rigor  mortis  often  absent.  The  blood,  usually  diffluent,  is  very  dark  and 
does  not  readily  acquire  the  scarlet-red  color  when  exposed  to  the  air.  There 
are  prominent  blood-stained  effusions  in  all  the  serous  sacks.  (Plate  V.)  Urine 
and  faeces  often  bloody.  Hemorrhages  beyond  the  local  lesion  much  more  conspicu- 
ous than  in  the  rapid  poisoning.  The  remote  lesions  of  slow  poisoning  resemble 
very  much  (morphologically)  the  primary  local  lesion,  but  are  not  so  extensive  or 
so  well  defined.  In  general  the  conditions  of  slow  venom  poisoning  resemble  those 
of  acute  septic  poisoning.  It  is  very  often  impossible  to  draw  a  distinct  line  between 
the  manifestations  of  rapid  and  slow  poisoning,  nevertheless  the  division  is  in  prac- 
tice convenient. 

One  case  of  very  protracted  slow  poisoning  was  observed  in  a  pigeon  which  had 
been  injected  with  venom  in  the  pectoral  muscle.  (See  Experiment  24,  Table 
Slow  Poisoning.) 

Instead  of  the  usual  gangrenous  change  there  was  seen  in  this  case  after  the 
lapse  of  two  weeks  a  decided  dry  atrophy  of  the  muscular  tissue  about  the  wound. 
Its  fibres  were  greatly  diminished  in  size  as  compared  with  the  opposite  unaffected 


1'ATHOLOGY.  141 

muscle,  and  many  of  them  were  entirely  disintegrated,  as  was  evident  from  the 
remnants  of  the  muscular  fibres  and  the  granular  material  which  took  their  place 
between  the  interstices  of  the  connective  tissue.  This  granular  material  was  seen 
throughout  the  specimen,  some  of  it  being  of  a  brown  tint,  and  probably  repre- 
senting disintegrated  blood  corpuscles.  The  internal  organs  were  all  in  a  state  of 
atrophy,  more  particularly  so  the  liver,  the  tissues  of  which  under  the  microscope 
bore  a  striking  resemblance  to  acute  yellow  atrophy.  The  serous  sacks  were  all 
largely  distended  by  blood  stained  serum.  The  heart  muscle  was  also  in  a  condi- 
tion of  atrophy,  its  chambers  empty,  and  the  blood  dark  and  not  coagulable. 
Blood  examined  microscopically  showed  appearances  to  be  mentioned  shortly. 

The  Effects  of  certain  Venoms  on  the  Coagulability  of  the  Blood. — One  of  the  most 
interesting  differences  in  the  action  of  the  venoms  of  the  Rattlesnake  and  Cobra 
and  which  was  pointed  out  some  years  ago  by  more  than  one  observer,  is  that 
the  former  venom  partially  or  completely  destroys  the  coagulability  of  the  blood, 
while  the  venom  of  the  Cobra  has  no  such  marked  effect.  The  blood  of  animals 
poisoned  with  Crotalus  venom  is  usually  thin  and  dark,  the  clots  form  slowly,  and 
are  very  soft  and  easily  broken  up. 

Some  direct  studies  were  made  to  test  more  accurately  this  interesting  property 
of  the  Crotalus  venom,  and  it  was  thus  observed  that  it  is  not  peculiar  to  the 
poison  of  this  genus,  but  is  also  a  characteristic  of  the  Moccasin.  Several  of  these 
observations  which  were  made  with  the  venom  of  the  Crotalus  adamanteus  we 
record  in  detail. 

Experiment. — Five  test-tubes  were  used : — 

No.  1  empty. 

No.  2  contained  ^  grain  dried  venom  dissolved  in  0.5  c.  c.  distilled  water. 

No.  3         "         |  "  in  1.0     "         " 

No.  4         "         ^  "  in  1.0     "         "  " 

No.  5  2  drops  glycerine  solution  of  venom,  equal  parts. 

These  test-tubes  were  packed  in  snow,  to  retard  coagulation  and  to  give  the  venom 
a  better  opportunity  to  act,  the  tubes  remaining  in  this  condition  for  about  half  an 
hour.  The  main  artery  in  the  leg  of  a  large  etherized  rooster  was  exposed,  and  a 
canula  placed  in  it.  The  blood  was  allowed  to  flow  into  the  tubes  in  the  order 
of  their  numbers,  the  tubes  being  gently  shaken  to  mix  the  venom  and  blood.  The 
operation  began  at  3:55  and  ended  at  4:00  p.  M.  At  4:35  the  tubes  were  ex- 
amined. The  blood  in  No.  1,  which  contained  no  venom,  was  firmly  clotted,  in  all 
the  others  the  blood  was  fluid.  At  4:55  the  test-tubes  were  all  taken  from  the 
snow.  Blood  in  No.  1  was  firmly  clotted  and  of  a  bright-red  color ;  blood  in  Nos. 
2,  3,  and  4  was  fluid  and  venous  in  appearance ;  blood  in  No.  5  was  fluid  and 
of  a  brighter  red  than  No.  1.  The  tubes  were  then  corked  with  raw  cotton  and 
set  aside. 

Twenty-four  hours  later  blood  in  No.  1  was  firmly  clotted,  in  Nos.  2  and  3  tarry, 
in  No.  4  tarry,  but  thinner  than  in  Nos.  2  and  3,  in  No.  5  perfectly  fluid ;  in  the 
lower  half  of  the  tube  was  a  mass  of  corpuscles,  while  the  upper  half  had  the  appear- 
ance of  pure  serum. 

Forty-eight  hours — no  appreciable  alteration. 


142  THE    VENOMS    OF    CERTAIN    THANATOPHIDE^E. 

Seventy-two  hours — no  appreciable  alteration;  the  blood  in  tube  No.  1  had  no 
unpleasant  odor,  but  all  the  rest  gave  decided  odors  of  putrefaction,  and  were  very 
dark. 

Comparative  observations  were  also  made  at  the  same  time  with  different  venoms, 
using  as  before  a  fowl  to  furnish  us  the  blood  and  the  snow  pack  to  retard  coagu- 
lation. 

In  test-tube  No.  1  was  placed  |  grain  dried  Moccasin  venom  in  1  c.  c.  distilled 
water. 

In  test-tube  No.  2  was  placed  |  grain  dried  Moccasin  venom  boiled  and  filtered 
through  clay. 

In  test-tube  No.  3  was  placed  \  grain  of  dried  Crotalus  venom  in  1  c.  c.  distilled 
water. 

In  test-tube  No.  4  was  placed  \  grain  of  dried  Crotalus  venom  in  1  c.  c.  distilled 
water,  heated  gradually  to  70°  C. 

In  test-tube  No.  5  was  placed  |  grain  dried  Cobra  venom  in  1  c.  c.  distilled  water. 

In  test-tube  No.  6  was  placed  |  grain  dried  Cobra  venom  in  1  c.  c.  distilled  water, 
boiled  and  filtered  through  a  clay  filter. 

In  test-tube  No.  7  nothing  was  placed  but  the  pure  blood. 

Into  each  of  the  test-tubes  about  10  c.  c.  of  blood  was  allowed  to  flow;  at  the 
end  of  15  minutes  the  blood  in  Nos.  2,  5,  6,  and  7  was  clotted  firmly,  and  the  blood 
in  Nos.  1,  3,  and  4  was  perfectly  fluid.  After  one  hour  and  a  quarter  the  blocd 
in  No.  1  was  clotted  in  a  quite  remarkable  clot,  which  was  exceedingly  elastic — the 
clot  when  picked  up  and  suspended  drew  out  into  a  long  worm-like  thread,  and 
could  then  be  further  pulled  out  to  at  least  double  its  length,  resuming  its  natural 
size  when  placed  upon  the  table.  The  blood  in  No.  3  had  some  very  soft  clots. 
In  No.  4,  the  blood  was  clotted  soft. 

On  the  second  day  all  of  the  bloods  were  firmly  clotted  except  Nos.  1,  3,  and  4, 
which  were  perfectly  fluid  and  had  a  putrefactive  odor,  which  was  absent  in  the 
others.  On  the  third  day  these  bloods  were  clotted  and  had  some  dark  serum, 
but  the  pure  blood  was  clotted  firmly  and  perfectly  dry  on  the  surface. 

From  these  observations  it  seems  clear  that  the  Cobra  venom  exerts  no  appreciable 
effect  on  the  coagulability  of  the  blood  of  a  chicken  when  thus  circumstanced,  and 
that  Crotalus  and  Moccasin  venoms  act  powerfully.  Moreover,  that  the  effect  of 
the  Crotalus  venom  is  the  more  efficient,  and  that  if  the  solutions  of  venom  have 
been  subjected  to  a  degree  of  heat  sufficient  to  coagulate  the  venom-globulins, 
the  effect  is  lessened  very  greatly.  It  thus  appears  that  the  principle  affecting 
the  coagulability  of  the  blood  is  most  largely  the  globulin. 

It  would  seem  therefore  that  venom-peptone,  although  not  without  power  to 
lessen  the  coagulability  of  blood,  has  not  the  full  efficiency  of  the  globulins. 
Neither  can  it  be  said  as  to  this  capacity,  that  the  small  percentage  of  Cobra 
globulin  has  even  relatively  the  anti-clotting  capacity  of  the  globulins  of  Crotalus. 

These  differences  between  Cobra  and  Crotalus  show  themselves  strikingly  in  the 
slighter  local  disorders  caused  by  the  Indian  serpent. 

The  singular  formation  of  an  elastic  clot  was  observed  in  other  cases.  It  ap- 
peared to  be  a  temporary  condition,  and  to  be  in  a  measure  due  to  the  great  increase 
in  the  adhesiveness  of  the  blood  corpuscles. 


PATHOLOGY.  143 


Microscopical  Changes  in  lie  Vurions  Ti-^m^  <>f  the  Body  from  the  Eft'ects  of  t/tr. 

V  1  11,0111  of  (  'rol«  I  a*. 

Effects  of  Fresh  Venom  vpon  the  Blood  Corpuscles.  —  A  series  of  experiments 
were  made  to  study  the  direct  as  well  as  the  remote  effects  of  the  venom  upon  the 
blood  corpuscles.  The  result  of  these  observations  was  the  discovery  of  some 
changes  which  have  not  been  heretofore  fully  described. 

A  drop  of  blood  from  man  or  any  mammal  treated  with  a  minute  quantity  of 
fresh  venom,  presented  the  following  appearances  under  the  microscope:  Upon 
the  white  blood  corpuscles,  the  venom  did  not  appear  to  have  any  other  effect  than 
to  stop  the  amoeboid  motion,  which  in  presence  of  venom  could  not  be  kept  up, 
even  by  the  use  of  the  warm  stage.  The  cells  appeared  somewhat  larger  than 
usual  and  also  more  granular.  The  red  blood  corpuscles  appeared  unchanged 
when  observed,  but  for  a  moment,  and  superficially,  yet  prolonged  and  careful 
study  revealed  very  remarkable  alterations.  The  alterations  in  the  red  blood  cor- 
puscles are  essentially  these  :  — 

The  blood  disks  lose  their  biconcavity  and  assume  a  spherical  form,  but  without 
parting  with  their  coloring  matter.  They  exhibit  also  great  adhesiveness,  arrang- 
ing themselves  into  various  sized  and  shaped  aggregations.  The  corpuscles  com- 
prising these  groups  sometimes  appear  to  fuse  so  that  their  outlines  cannot  be 
determined,  even  by  high  amplification.  In  addition  the  corpuscles  seem  to  soften 
and  acquire  a  peculiar  ductility  and  capacity  to  be  stretched  without  fracture.  By 
inclining  the  stage  of  the  microscope,  or  making  gentle  pressure  upon  the  cover- 
glass,  allowing  thereby  the  liquid  to  flow,  the  red  blood  corpuscles  may  be  seen  to 
elongate  themselves  into  spindle-shaped  or  even  into  fine  thread-like  bodies. 
(Figs.  1  and  2,  Plate  III.,  and  Plate  IV.)  Such  masses  of  corpuscles  appear  to  act 
like  colloid  material. 

One  drop  of  human  blood  was  mingled  with  one  of  fresh  snake  venom  by  the 
application  of  the  cover-glass.  The  three  fields  photographed  were  found  in  the 
zones  of  contact  between  the  blood  and  venom  ;  they  occurred  within  a  small  area  — 
almost  adjacent.  Fields  1,  2,  and  3,  Plate  IV.,  were  photographed  respectively 
within  15,  30,  and  40  minutes  after  the  first  application  of  the  venom  to  the 
blood.  As  the  masses  of  corpuscles  were  slowly  changing  form  and  position,  the 
exposure  was,  necessarily,  but  for  a  part  of  a  seoond.  The  lens  empfoyed  was 
Spencer  ^  immersion,  giving  400  diam.  with  the  low  power  eye-piece. 

This  remarkable  condition  seems,  however,  to  be  only  temporary,  and  in  fact 
often  escapes  observation.  After  a  short  time,  which  in  about  100  observations 
was  found  to  vary  from  a  few  seconds  to  a  quarter  of  an  hour,  the  apparently 
homogeneous  blood-cell  masses  break  up  anew  into  individual  corpuscles,  which 
then  continue  isolated  or  in  bead-like  rows,  but  remain  spheroidal,  i.  e.,  do  not 
regain  their  biconeal  shape. 

Those  corpuscles  which  arrange  themselves  in  rows  present  an  appearance  strik- 
ingly different  from  the  ordinary  rouleaux  arrangement  of  normal  blood-disks,  an 
appearance  which  may  better  be  designated  as  "beaded,"  because  the  corpuscles 
are  here  spheroidal  and  not  disk-like. 


144  THE   VENOMS    OF   CERTAIN   THANATOPHIDE./E. 

Liquids  in  general  variously  modify  the  shape  of  the  red  blood-disks,  but  no 
liquid  or  reagent  tried  in  control  experiments  produces  the  effects  described 
above. 

Watery  solutions  of  dried  venom  did  not  exhibit  the  immediate  influence  upon 
the  red  blood  corpuscles  as  well  as  the  fresh  venom,  although  the  corpuscles  very 
promptly  became  spheroidal  as  they  do  from  most  watery  liquids ;  but  did  not  lose 
the  coloring  matter  as  when  exposed  to  pure  water  without  venom. 

The  blood  of  birds,  upon  being  mixed  with  venom,  does  not  show  the  above 
described  changes  in  as  striking  a  manner  as  mammalian  blood.  The  nuclei  of 
the  oval  corpuscles  of  the  pigeon  appear,  however,  to  undergo  a  rapid  necrotic 
change  which  finally  gives  rise  to  a  granular  albuminoid  material  to  be  seen 
floating  in  large  quantities  between  the  corpuscles. 

A  number  of  experiments  were  made  to  study  the  changes  in  the  corpuscles  of 
the  living  animal.  Fresh  venom  or  solutions  of  dry  Crotalus  venom  were  injected 
hypodermatically,  and  then  the  blood  taken  at  intervals  from  the  local  lesion  as 
well  as  from  the  general  circulating  fluid  and  examined  under  the  microscope. 

The  blood  taken  from  local  lesions  presented  quite  often  alterations  in  the  cor- 
puscles similar  to  those  observed  in  a  direct  mixture  of  blood  and  venom  under  the 
microscope,  as  described  above.  It  was  not  possible,  however,  to  trace  all  the 
modifications  of  the  red  blood  corpuscles  in  specimens  of  the  circulating  blood; 
only  one  change  being  constant,  viz.,  the  spheroidal  transformation  of  the  blood 
disks.  The  red  blood  corpuscle  retained  the  acquired  spherical  shape  after  the 
death  of  the  animal.1 

All  the  experiments  made  in  order  to  study  the  ultimate  changes  in  the  blood- 
corpuscles  gave  nearly  similar  results  varying  slightly  in  degree  with  the  quantity 
of  the  venom  and  the  animal  employed.  The  record  of  one  observation  will  suffice 
for  all. 

Experiment. — Young  cat.  Injected  at  2  P.  M.  3  m.  m.  fresh  Crotalus  venom  in 
left  thigh.  Hair  of  part  being  previously  clipped  away. 

2  minutes  later.  Animal  well.  Blood  microscopically  examined.  Local  lesion ; 
blood-disks  assuming  spherical-shape.  Blood  from  auricular  artery  showed  no 
changes  in  the  blood-disks. 

5  minutes  later.  Animal  well.  Local  lesion  ;  blood-disks  all  spherical  showing 
also  gelatinoid  behavior  and  ductility  on  pressure.  Auricular  artery,  blood-disks 
normal. 

8  minutes  later.  Animal  restless.  Local  lesion  shows  only  spherical  shape  of 
red  blood-disks.  Auricular  artery  also  shows  partial  change  of  red  blood-disks  to 
spherical  shape. 

12  minutes  later.  Animal  ill.  Blood  of  local  lesion  as  well  as  blood  taken  from 
jugular  vein  shows  same  changes  as  when  last  examined. 

1  Errors  in  distinguishing  the  spheroidal  shape  of  the  red  blood-corpuscles  from  the  round  shape 
which  the  normal  disk-like  corpuscles  exhibit  when  viewed  in  a  certain  .position  are  easily  eliminated 
when  the  blood  is  brought  into  current  by  gentle  pressure  upon  the  cover-glass,  or  by  inclining  the 
stage  of  the  microscope.  The  disks  assuming  spheroidal  shape  are  decidedly  reduced  in  diameter 
and  appear  smaller. 


PATHOLOGY.  145 

20  minutes  later.  Animal  quite  ill.  lied  blood-disks  all  spheroidal  when  exam- 
ined in  the  local  lesion  and  in  several  other  parts  of  the  body. 

25  minutes  later.     Animal  dead. 

30  minutes  later.  Blood  examined  from  heart.  All  the  red  blood-disks 
spherical. 

24  hours  later.  The  dead  animal  being  kept  in  a  cool  place,  lied  blood-disks 
all  spherical  and  many  disintegrated. 

The  blood,  in  sections  of  tissues  from  animals  poisoned  with  venom,  also  presents 
decided  alterations.  The  corpuscles  in  tissues  hardened  with  preserving  fluid  are 
seldom  seen  intact.  When,  however,  the  parts  in  question  are  placed  in  preser- 
vative fluid  immediately  after  the  death  of  the  animal  the  spheroidal  (altered)  red 
blood  corpuscles  may  be  distinguished ;  and  still  more  likely  are  they  to  be  intact 
if  the  animal  was  killed  before  the  venom  had  asserted  its  fatal  effect. 

The  corpuscles  as  a  rule  appear  disintegrated  in  animals  dead  from  slow  Crotalus 
venom  poisoning,  and  present  themselves  as  a  granular  debris  of  a  yellowish  or  dark 
brown  color.  The  tissue  elements  of  the  part  into  which  the  venom  had  been 
directly  injected  are  as  a  rule  profusely  saturated  with  the  coloring  matter  of  the 
blood.  The  microscope  further  reveals  blood  crystals  and  numerous  bacteria 
between  and  within  the  tissue  elements.  This  indicates  the  profound  altera- 
tion which  takes  place  in  the  blood  in  venom  poisoning,  and  accounts  for  the 
black  appearance  and  the  rapid  putrefactive  changes  which  are  seen  in  the  local 
lesion. 

"Quite  recently  Lacerda,  in  lectures1  on  snake  poisons,  speaks  of  alterations  of 
the  blood,  which  differ  much  from  those  observed  by  us.  He  does  not  state  the 
serpent  venom  employed.  It  was  presumably  from  the  Bothmps  uriitu,  Lacer. 
In  slow  poisoning,  he  says,  the  blood  globules  become  indented  like  a  toothed 
wheel.  Some  are  elongated,  deformed,  or  broken  up;  others  present  shining  points 
and  then  break  up  into  minute  fragments.  Some  undergo  a  change  of  tint  to 
chesnut  brown,  others  become  entirely  discolored. 

"  The  consequences  of  mixing  pure  blood  and  pure  venom,  he  says,  are  these : 
The  red  blood-globules  unite  in  mass,  adhere  one  to  the  other  and  begin  thereon 
to  lose  their  normal  forms.  In  a  few  minutes  the  dissolution  is  complete.  There 
remains  only  an  amorphous  protoplasmic  matter,  semi-liquid,  diffluent,  of  a  uni- 
form yellow  color,  with  well-marked  red  striations.  After  some  minutes  the  hema- 
tine  or  coloring  matter  quite  disintegrated  is  seen  under  the  form  of  granular 
substance  of  a  deep  vermillion  red.  Whilst  the  globules  thus  break  up  bubbles  of 
gas  rise  here  and  there." 

We  have  quoted  this  account  nearly  in  full  to  point  out  that  it  describes  a 
sequence  of  appearances  very  unlike  those  which  we  have  delineated. 

Effects  of  the  Venom  upon  certain  Tissues. — Direct  observations  were  further  made 
as  to  the  effects  of  venoms  upon  the  various  solid  tissues,  such  as  the  bloodvessel 
walls;  muscular  tissue,  unstriated  and  striated;  nervous  tissue  (brain  and  medulla 

1  Le9ons  sure  le  Venin  des  Serpentes  du  Br^sil,  etc.  J.  B.  De  Lacerda,  pp.  87-88.  Rio  de 
Janeiro,  1884. 

19       June,  1886. 


146  THE    VENOMS   OF   CERTAIN    THANATOPHIDE^E. 

oblongata)  ;  lungs,  liver,  skin,  mucous  membranes,  the  cornea,  spermatozoa  and 
ciliated  epithelium,  and  most  extensively  upon  the  mesentery  and  other  serous 
membranes. 

If  fresh  venom  be  injected  into  any  organ  or  applied  to  any  internal  part  of  the 
body,  one  of  the  chief  effects  is,  as  Dr.  Weir  Mitchell  showed  twenty-two  years  ago, 
the  production  of  minute  hemorrhages. 

The  studies  reported  here  thoroughly  confirm  Dr.  Mitchell's  observations. 
Above  all,  it  was  further  evident  that,  as  a  general  rule,  it  was  everywhere  the 
parencliymatous  elements  of  the  organ  or  parts  that  underwent  necrotic  changes 
{which  will  be  described  below},  while  the  interstitial  elements  of  organs  or  tissues 
acted  upon  by  the  venom,  remained  usually  unaffected,  or  were  merely  infiltrated  with 
blood,  or  with  the  disintegrated  products  of  blood. 

Effects  of  Venom  upon  Bloodvessel  Walls. — If  fresh  venom  be  applied  to  a  vascular 
tissue  and  watched  under  the  microscope,  no  effect  upon  any  of  the  larger  blood- 
vessels is  perceptible.  It  appears  that  the  venom  even  after  prolonged  contact  has 
no  visible  influence  upon  the  smooth  muscular  tissue  constituting  the  middle  coat 
of  arteries  and  veins.  The  adventitia  of  such  vessels  also  offer  considerable 
resistance,  although  the  vasa  vasorum  become  extremely  congested.  Even  small 
arterioles  and  venules  are  unaffected. 

The  capillary  bloodvessels,  however,  having  a  mere  endothelial  wall  surrounded 
by  a  delicate  adventitia  show  a  decided  change  upon  the  application  of  venom. 
The  endothelium  constituting  the  capillary  wall  becomes  cloudy  and  looks  as  if 
roughened  and  displaced,  and  though  no  actual  rupture  of  the  vessel  is  demon- 
strable to  the  eye  a  diapedesis  of  blood-corpuscles  and  a  leakage  of  serum  occurs, 
and  this  process  is  sometimes '  amazingly  rapid.  As  will  be  described  later  with 
more  details,  the  following  are  the  essential  points  in  the  action  of  the  venom  upon 
its  direct  application  to  a  vascular  membrane  viewed  under  the  microscope.  The 
blood  current  appears  at  first  to  be  accelerated,  and  the  color  of  the  blood  becomes 
darker.  Then  in  a  few  moments  while  the  circulation  still  continues  in  the  veins 
and  arteries,  in  many  of  the  capillaries  stagnation  occurs.  From  these  latter  vessels, 
and  apparently  only  from  them,  the  blood  oozes,  first  forming  pin-point  ecchymoses 
which  gradually  increase,  and  which  by  fusion  give  rise  at  last  to  a  general  hemor- 
rhagic  infiltration  of  the  neighboring  tissues. 

Changes  in  the  Striped  Muscular  Tissues. — Venom  directly  applied  to  living 
striped  muscular  tissue  produces  changes  which  become  apparent  immediately  after 
the  death  of  the  animal.  The  ultimate  muscular  fibrilla?  readily  break  up  into  their 
sarcous  elements,  these  becoming  easily  separable  in  transverse  layers,  the  so-called 
Bowman's  disks.  A  granular  change1  of  the  elements,  not  however  uniform  in 
character  and  distribution,  is  quite  conspicuous.  (Fig.  3.)  It  should  be  noted  that 
all  these  changes  occur  without  the  addition  of  any  other  reagent  than  venom  and 
become  conspicuous  when  the  poisoned  tissue  is  teased  out  in  water. 

The  alterations  just  referred  to  are  most  manifest  in  muscular  fibres  near  or 
around  which  the  capillaries  are  affected  by  the  venom,  localities  apt  to  be  marked 

1  Figured  by  Dr.  Mitchell,  in  his  first  essay. 


PATHOLOGY. 


147 


by  the  presence  of  extravasated  blood.     The  changes  described  are  not  uniform, 
even  in  an  individually  affected  fibre,  but  are  bounded  by  small  abrupt  layers  of 

Fig.  3. 


normal  sarcous  elements,  the  whole  being  surrounded  by  an  unaffected  sarco- 
lemma.  The  latter,  which  is  beautifully  demonstrated  on  such  occasions,  shows 
constrictions  in  those  places  where  the  sarcous  elements  are  disintegrated.  (See 
Figs.  3  and  4.) 

Fig.  4. 


All  muscular  fibres  of  the  part  where  the  poison  was  injected  are  more  or  less 
granular,  and  are  often  stained  by  hematin.  The  granular  material  between  the 
fibres  has  very  much  the  appearance  of  micrococci,  but  by  appropriate  tests  only  a 
small  proportion  of  the  granules  can  be  identified  as  bacteria.  The  remaining 
granular  matter  can  be  identified  as  particles  of  necrosed  sarcous  elements,  dis- 
integrated blood,  and  granular  substances  which  have  been  described  as  constituents 
of  the  fresh  venom  and  introduced  from  without.  These  granular  muscle  changes 
occur  only  in  or  near  the  wound,  and  not  also  in  remote  muscles.  They  demand 
for  their  production  a  certain  length  of  time,  and  are  most  decided  in  cases  of  long 
survival. 

Changes  in  the  Lungs. — As  has  been  seen  from  the  table  of  experiments,  the 
injection  of  venom  into  the  lungs  was  followed  by  nearly  instantaneous  death. 
The  local  lesion  was  an  hemorrhagic  infarction  throughout  the  whole  of  the  paren- 


148  THE    VENOMS    OF    CERTAIN    THANATOTHIDE^. 

chyma,  filling  also  all  of  the  air  vesicles.  There  were  extensive  snh-pleural  ecchy- 
moses,  both  parietal  and  visceral,  as  well  as  sub-pericardial  ecchymoses.  Under  the 
microscope  with  high  amplication  sections  of  the  lung  tissue  showed  a  peculiar 
clogging,  fusion,  and  ductility  of  the  red  blood-corpuscles  not  unlike  that  which 
follows  the  application  of  fresh  venom  to  the  blood. 

This  appearance  is,  however,  not  uniform,  as  in  many  places  the  corpuscles  are 
merely  spheroidal,  or  have  undergone  a  granular  disintegration.  The  bloodvessels 
are  all  highly  congested,  the  air  vesicles  seem  to  be  distended  by  extravasated  blood. 
The  micrococci  introduced  with  the  venom  appear  to  have  rapidly  multiplied, 
numerous  masses  being  seen  in  the  air  vesicles  and  in  the  more  necrosed  parts  of 
the  lung  tissue.  In  general  the  tissue  is  deeply  stained  by  the  coloring  matter  of 
the  blood. 

Brain  and  Medulla  Ol>longata. — If  a  minute  quantity  of  venom  was  successfully 
injected  directly  into  the  cranial  cavity  of  a  pigeon,  the  animal  fell  immediately  and 
expired  in  a  few  minutes.  The  pia  mater  was  preeminently  the  seat  of  hemor- 
rhages, and  blood  was  also  seen  to  fill  the  peri-vascular  spaces  of  many  of  the  cere- 
bral vessels.  The  cerebral  tissue,  and  particularly  the  nerve  elements,  showed  a 
granular  change  analogous  to  that  observed  in  muscular  tissue,  and  similar  appear- 
ances were  noted  from  the  effects  of  the  venom  upon  the  medulla  oblongata  and 
spinal  cord.  Where  animals  were  poisoned  by  introducing  the  venom  subcuta- 
neously  into  some  other  part  of  the  body,  minute  capillary  hemorrhages  were 
also  observed  in  the  membranes  of  the  brain,  and  in  two  instances  ecchymoses 
were  noted  in  the  substance  of  the  medulla  oblongata,  although  as  a  rule  only 
intense  congestion  of  its  vessels  was  seen.  .The  bloodvessels  were  so  much 
distended  with  blood  as  to  be  double  or  even  triple  their  normal  calibre,  fully 
obliterating  the  perivascular  spaces  and  unquestionably  exerting  much  pressure 
upon  the  surrounding  nerve  elements. 

Effects  of  (lie  Venom  when  applied  to  Uninjured  Mucous  Menibranes,  and  upon  the 

Cornea. 

The  following  experiments  were  made : — 

Experiment. — Adult  albino  rabbit,  etherized.  A  drop  of  an  aqueous  solution  of 
the  dried  venom  Crotalus  adamanteus  was  dropped  on  the  cornea  and  conjunctiva 
of  the  left  eye.  In  a  few  minutes  the  conjunctiva  became  ecchymosed  and  cede- 
matous  to  such  an  extent  as  to  close  the  eyelids.  Animal  died  in  five  hours.  After 
death  the  conjunctiva  and  eyelids  were  seen  to  be  soaked  with  extravasated  blood, 
while  the  cornea  remained  perfectly  transparent  and  colorless,  showing  no  trace  of 
inflammatory  change  when  removed  and  examined  under  the  microscope. 

Post-mortem  examination  showed  extensive  sub-pleural,  sub-peritoneal,  and  slight 
sub-arachnoid  ecchymoses. 

Experiment. — Young  kitten,  etherized.  A  drop  of  fresh  venom  was  placed  on 
the  cornea.  Results,  similar  to  those  of  foregoing  experiments,  the  cornea  remain- 
ing transparent,  but  exhibiting  a  certain  roughness  upon  the  surface,  which  under 
the  microscope  proved  to  be  due  to  slight  desquamation  of  the  epithelium. 


PATHOLOGY.  •     U9 

Experiment. — Young  kitten,  etherized.  Abdominal  cavity  and  stomach  opened 
and  fresh  venom  applied  to  surface  of  mucous  membrane.  Specimen  watched  for 
half  an  hour  tailed  to  reveal  any  decided  visible  changes,  beyond  a  slight  corruga- 
tion and  congestion.  No  ccchymoses. 

The  Effect  of  Crotahis  Venom.  v/><»t,  Ciliary  Motion. — Fresh  venom  applied  to 
ciliated  epithelium  taken  from  the  edge  of  the  tunic  of  a  fresh  oyster  seemed  to 
exert  no  effect  upon  ciliary  motion,  The  specimen  was  watched  and  compared 
with  the  control  experiment  side  by  side.  The  cilia?  still  kept  up  their  movement 
at  the  end  of  three  hours  in  both  specimens. 

Fresh  venom  was  applied  to  ciliated  epithelium  taken  from  the  pharynx  of  a  live 
frog.  The  specimen  was  carefully  observed  and  compared  with  similar  preparations 
in  which  venom  was  not  used.  In  the  latter  the  ciliary  motion,  as  a  rule,  kept  up 
longer.  Yet  after  one  hour  specimens  treated  with  venom  continued  to  exhibit 
motion  though  less  vigorous  than  in  the  control  specimens. 

The  Effect  of  Venom  upon  Spermatozoa. —  Fresh  venom  applied  to  spermatozoa 
taken  from  a  live  rabbit  seemed  to  exert  a  decided  influence.  Specimens  treated  with 
the  venom  were  examined  side  by  side  with  control  specimens,  and  while  in  the 
presence  of  venom  the  spermatozoa  ceased  to  exhibit  their  peculiar  movements  in 
from  one-quarter  to  three-quarters  of  an  hour,  unpoisoned  spermatic  particles  con- 
tinued to  move  for  many  hours.  The  venom  did  not  appear  to  produce  any  changes 
in  the  substance  or  the  bodies  of  the  individual  spermatozoa.1 

The  Mechanism  of  the  Hemorrhages  as  Observed  in  Venom  Poisoning. 

In  order  to  study  the  mechanism  of  the  hemorrhages  Dr.  Mitchell's  original  ob- 
servations were  repeated  as  follows:  — 

The  animals  used  were  cats,  rabbits,  pigeons,  white  rats,  and  frogs.  The  frogs 
do  not  give  satisfactory  results  as  they  withstand  the  effects  very  strenuously  and 
if  peritoneal  hemorrhages  occur  at  all  they  are  very  scanty.  The  most  satisfactory 
observations  were  obtained  when  cats  were  employed,  as  these  animals  lived  longest 
after  the  application  of  the  venom,  the  latter  also  acting  more  slowly,  thus  permit- 
Ling  satisfactory  study  of  the  effects  under  the  microscope. 

Anaesthetics  were  always  used.  Ether  was  found  to  give  the  best  results. 
Chloral  appeared  to  retard  the  effects  of  the  venom.  While  in  an  etherized 
animal  peritoneal  hemorrhages  appeared  at  once  upon  the  application  of  the 
venom,  in  a  chloralized  animal  they  occurred  much  later,  and  sometimes  failed 
to  appear. 

A  few  drops,  three  to  six,  of  a  saturated  solution  of  chloral  hydrate  were  usually 
sufficient  to  anaesthetize  a  small  kitten  or  rabbit,  two  drops  for  a  white  rat,  one  drop 
for  a  mouse.  It  was  administered  hypodermatlcally.  In  administering  ether  the 
animal  was  placed  under  a  bell-glass,  with  a  sponge  kept  saturated  with  the  agent 
until  the  animal  was  rendered  powerless. 

In  experiments  upon  the  mesentery  to  be  examined  under  the  microscope,  the 

1  The  observations  were  made  under  an  amplification  of  one  thousand  diameters. 


150  THE    VENOMS    OF    CERTAIN   THANATOPHIDE^E. 

animal  was  placed  on  its  right  side  upon  a  thin  oblong  wooden  board.  On  one 
side  of  the  board  near  the  middle  was  cut  a  triangular  opening,  each  side  being 
about  one  inch  in  length.  An  incision  was  then  made  in  the  median  line  through 
the  abdominal  integuments,  sufficiently  large  to  allow  a  loop  of  the  intestine  to  be 
extracted.  Care  was  taken  that  pressure  should  not  interfere  with  the  circulation. 
The  loop  being  drawn  out,  it  was  stretched  over  the  hole  in  the  board  above  described, 
and  kept  in  position  by  means  of  pins. 

The  venom  was  applied  to  the  uninjured  surface  of  the  mesentery.  A  saturated 
aqueous  solution  of  the  dried  venom  was  most  commonly  used.  The  moist  chamber 
was  not  required,  as  the  experiments  were  of  short  duration.  The  warm  stage 
seemed  only  to  hasten  the  process  and  otherwise  was  observed  to  have  no  special 
influence,  being  rather  disadvantageous. 

Experiment  1. — A  young  kitten  was  secured  by  means  of  ether  as  above  described, 
and  placed  upon  the  microscopic  stage.  A  few  drops  of  an  aqueous  solution  of  the 
venom  were  allowed  to  flow  over  the  mesentery.  The  part  being  carefully  watched 
with  the  naked  eye,  it  was  noticed  that  after  one  minute  tiny  hemorrhagic  points 
made  their  appearance  here  and  there,  all  over  that  part  of  the  mesentery  which 
was  under  the  direct  influence  of  the  venom.  These  hemorrhages  increased  rapidly 
in  size,  and  in  a  few  minutes  the  whole  surface  became  the  seat  of  one  diffused 
hemorrhagic  infiltration.  (Plate  III.,  Figs.  3,  4,  5,  6,  7.) 

Experiment  2. — Young  white  rat.  Ether.  Aqueous  solution  of  venom  applied 
as  before  to  the  mesentery.  The  loop  of  the  mesentery  acted  upon  was  quickly 
cut  out  by  means  of  scissors  after  the  lapse  of  one  minute  and  subjected  to  drying. 
A  beautiful  preparation  was  thus  obtained,  in  which  the  minute  hemorrhages  were 
permanently  fixed  by  drying,  preserving  their  natural  appearance.1 

Experiment  3. — Young  kitten.  Chloral.  Mesentery  spread  upon  microscopical 
stage.  An  aqueous  solution  of  dried  venom  applied  in  the  same  manner  as  above. 
In  this  case  the  hemorrhages  did  not  appear  so  promptly  and  we're  not  so  rapid  in 
their  development.  Nearly  five  minutes  elapsed  before  they  began  to  form. 

Experiment  4. — Young  white  rat.  Chloral.  Venom  applied  as  in  preceding 
experiments ;  there  seemed  to  be  delay  in  the  appearances  and  development  of  the 
hemorrhages. 

Further  enumeration  of  this  class  of  observation  is  unnecessary,  as  more  than 
forty  experiments  exhibited  the  characteristic  hemorrhages,  except  in  the  case  of 
frogs.  Five  of  the  latter  were  used. 

It  was  noted  that  chloral  always  retarded  the  production  of  hemorrhages,  at 
least  they  did  not  appear  as  rapidly  as  when  ether  was  used. 

Microscopical  Details. — It  being  necessary  to  study  the  exact  location  of  the 
hemorrhages  and  the  mode  of  the  escape  of  blood,  the  following  modifications  of 
methods  were  adopted  in  repetition  of  the  older  experiments  of  Dr.  Mitchell. 

1  After  much  experimentation  this  method  of  preparing  permanent  specimens  was  fonnd  to  be  the 
only  available  one.  Specimens  of  mesentery  mounted  in  any  kind  of  liquid  very  soon  lose  their 
proper  appearance,  as  the  hemorrhagic  specks  in  the  membrane  gradually  vanish,  or  get  blurred  from 
the  effects  of  the  preserving  fluid. 


PATHOLOGY.  151 

Experiment  5. — Cat.  Ether.  Mesentery  exposed  and  placed  on  the  stage  of 
the  microscope.  The  aqueous  solution  of  venom  was  applied,  and  the  experiment 
watched  under  a  magnifying  power  of  GO  diameters.  In  thirty  seconds  minute 
hemorrhagic  points  were  noticed  as  in  all  the  previous  experiments  first  along 
the  sides  of  the  smallest  capillaries.  It  was  also  observed  that  the  hemor- 
rhages occurred  first  in  those  small  capillaries  which  were  in  the  neighborhood  of 
larger  vessels.  In  vascular  plexuses  which  started  from  the  greater  arteries  the 
hemorrhages  appeared  much  sooner  than  in  those  which  took  their  departure 
from  smaller  arterioles.  In  each  case,  however,  it  was  only  the  capillaries  from 
which  the  hemorrhages  proceeded,  the  arteries  and  veins  remaining  intact.  The 
hemorrhages  being  seen  to  proceed  from  capillaries  in  the  vicinity  and  along  the 
route  of  larger  vessels,  one  may  erroneously  get  the  impression  that  it  is  the  latter 
from  which  the  bleeding  arises.  No  actual  breech  of  continuity  in  the  capillaries 
was  observed,  and  it  appeared  as  though  the  blood  filtered  through  the  walls  of 
these  minute  channels. 

Experiment  6. — Kitten.  Ether.  Mesentery  exposed  in  the  usual  manner.  The 
mesenteric  vessels,  both  the  main  artery  and  the  veins,  were  ligated  near  the  root  of 
the  mesenteric  attachments.  A  salt  solution  stained  by  aniline  blue  was  injected 
into  the  vein.  The  venom  was  applied,  and  the  field  closely  watched  under  the 
microscope.  No  extravasation  of  the  injected  solution  or  of  blood  could  be  observed. 

Experiment  7. — Kitten.  Ether.  Vessels  ligated  and  salt  solution  with  aniline 
injected  as  in  previous  experiment.  Applied  aqueous  solution  of  the  dry  venom. 
No  extravasation  of  the  colored  liquid  or  blood  observed. 

Experiment  8. — Kitten.  Animal  secured  as  before,  but  no  salt  solution  injected. 
Mesenteric  veins  and  the  artery  ligated  near  root  of  mesentery.  Solution  of  dried 
venom  applied.  Hemorrhage  as  usual,  but  slow  and  scanty. 

Experiment  9. — Kitten.  Ether.  Animal  fixed  as  in  last  experiment  upon 
microscopical  stage.  Fresh  venom  applied  and  watched  for  one-half  hour.  Hemor- 
rhages were  seen  to  develop  more  slowly. 

Experiment  10. — Kitten.  Ether.  Mesenteric  vein  and  artery  ligated  as  in  pre- 
ceding experiments.  Fresh  venom  applied  as  before,  and  a  marked  delay  in  de- 
velopment of  hemorrhages  again  observed. 

Experiment  11. — Kitten.  Ether.  Mesenteric  vessels  tied  not  only  at  the  root 
of  the  mesentery,  but  also  peripherally  at  the  convex  portion  of  the  loop,  thus 
almost  entirely  cutting  off  the  circulation.  Fresh  venom  applied.  Hemorrhages 
were  scarcely  appreciable  with  the  naked  eye. 

Experiment  12. — Kitten.  Ether.  Mesenteric  vessels  tied  at  both  root  and  peri- 
phery of  mesentery.  Venom  applied  immediately.  Hemorrhage  hardly  perceptible. 

The  above  experiments  were  subsequently  repeated,  especially  those  in  reference 
to  the  effects  of  the  venom  upon  bloodvessels  when  blood  had  been  substituted 
by  a  0.75  per  cent,  saline  solution.  These  experiments,  however,  gave  the  same 
results  as  those  just  described,  and  hence  it  is  unnecessary  to  occupy  space  in  multi- 
plying similar  records.  Yet  some  studies  in  the  same  direction  have  been  left 
undone.  It  might  be  desirable  to  elaborate  the  methods  of  experimentation,  e.  g., 
by  application  of  artificial  blood  pressure,  etc.  In  all  the  experiments  above  quoted. 


152  THE   VENOMS   OF   CERTAIN   THANATOPHIDEyE. 

except  in  experiments  6  and  7  (where  the  blood  was  substituted  by  another  liquid), 
the  peculiar  extravasations  of  blood  followed  the  application  of  the  venom. 

"When  the  mesenteric  vessels  were  tied  as  in  experiments  8,  9,  and  10,  there  was 
a  delay  in  the  appearance  of  the  hemorrhages.  When  the  vessels  were  tied  in  two 
places,  as  in  experiments  11  and  12,  so  as  to  cut  off  the  circulation  in  a  great 
measure,  the  hemorrhages  appeared  hardly  appreciable  to  the  naked  eye.  And  as 
we  have  seen  above,  there  was  no  extravasation  at  all  when  the  blood  was  substi- 
tuted by  an  artificial  liquid,  as  in  experiments  6  and  7. 

Therefore,  the  hemorrhagei  become  less  marked  in  proportion  to  the  interference 
with  the  circulation  of  the  blood  in  the  part. 


GENERAL   CONSIDERATIONS.  153 


CHAPTER    XI. 

GENERAL  CONSIDERATIONS. 

IT  seems  desirable  at  the  close  of  a  research  such  as  we  here  record  to  offer  a 
few  brief  and  general  considerations  in  connection  with  some  of  the  methods  and 
plans  pursued  in  parts  of  the  work,  to  group  some  of  the  conclusions,  and  to  bring 
together  deductions  which  are  necessarily  scattered.  A  summary  is  also  desirable 
that  we  may  set  forth  succinctly  the  essential  actions  of  venom  so  as  to  make  clear 
the  important  differences  in  the  toxic  influences  of  globulins  and  peptones,  to  facili- 
tate the  application  of  what  we  have  learned  to  the  treatment  of  snake  bite,  and  to 
indicate  new  lines  of  research  in  the  most  promising  directions. 

Our  discovery  of  the  existence  of  two  distinct  classes  of  poisons  in  venoms,  that 
both  are  doubtlessly  represented  in  all  venoms,  only  differing  in  relative  propor- 
tions and  slightly  in  chemical  and  physiological  properties,  that  they  possess 
activities  akin  but  yet  readily  distinguished,  and  that  they  are  proteids  and  closely 
related  to  principles  normally  existing  in  mammalian  blood,  seems  to  us  as  of 
grave  importance.  Our  methods,  however,  for  the  separation  of  the  poisonous 
substances  in  venoms  are  open  to  improvement,  because  the  processes  are  slow, 
and  since  possibly  one  of  the  poisons  at  least  is  injured.  It  does  not  seem  from 
the  results  of  our  physiological  studies  with  these  poisons  that  any  of  them  except- 
ing the  copper-venom-glolnlin  have  suffered,  but  that  this  has  been  affected  seems 
probable  from  its  altered  solubility,  its  comparatively  low  toxic  power,  and  its 
physiological  peculiarities  compared  with  the  other  globulins.  Doubtless  the 
ordinary  methods  for  the  separation  of  the  globulins  from  other  proteids  in  solu- 
tion could  be  used  to  advantage,  but  how  far  successful  they  may  prove  in  isolating 
the  globulins  from  each  other  can  only  be  determined  by  extended  and  careful 
investigation. 

The  plan  we  adopted  in  studying  venoms  and  their  active'  principles  on  the 
arterial  pressure,  pulse,  and  respiration  is  probably  open  to  much  criticism,  but  any 
other  course  seemed  unavoidable.  Instead  of  studying  all  venoms  together  as 
though  they  were  absolutely  identical  compounds,  although  from  different  sources, 
and  each  of  the  active  elements,  as  for  instance  the  peptones,  together  as  identical, 
it  would  doubtless  have  been  preferable  to  have  made  a  detailed  investigation  of 
each  venom,  and  of  each  of  the  active  principles  of  that  specimen.  But  this  course 
could  not  have  been  pursued  satisfactorily  because  of  the  meagre  supply  of  poison. 
It  was  then  simply  a  question  as  to  whether  we  would  take  a  very  limited  number 
of  experiments  with  each  venom  and  each  of  its  active  principles,  and  base  conclu- 
sions thereon,  or  study  the  actions  of  all  pure  venoms  together,  of  all  the  water- 

20       June,  1886. 


154      THE  VENOMS  OF  CERTAIN  TH  A  N  AT  O  P  H  I  DE  M. 

venom-globulins  together,  etc.,  and  then  form  our  conclusions.  The  latter  course 
seemed  preferable :  first,  because  of  the  similarity  in  the  actions  of  all  pure  venoms 
and  of  the  ready  interpretation  of  any  differences,  and  of  the  resemblance  in  the 
actions  of  members  of  each  of  the  classes  of  poisons ;  second,  because  in  some  of 
the  actions  such  diverse  factors  are  at  work  as  to  give  apparently  contradictory 
results,  so  that  conclusions  founded  upon  a  very  limited  number  of  experiments 
would  likely  be  more  misleading  than  in  the  plan  we  adopted. 

We  summarize  the  following  important  points,  deduced  chiefly  from  our  studies 
of  Crotalus  venom,  to  which  are  added  a  few  comments : — 

1.  Venoms  bear  in  some  respects  a  strong  resemblance  to  the  saliva  of  other 
vertebrates. 

2.  The  active  principles  of  venom  are  contained  in  its  liquid  parts  only.     The 
solid  constituents,  such  as  we  observed  suspended  in  the  poison,  consist  of  epithe- 
lium cells,  some  minute  rod-like   animal  organisms   and  micrococci,  etc.,  which, 
when  separated  from  the  liquid  fresh  venom  by  means  of  filtration  and  well  washed 
by  water  are  harmless.     Micrococci  are  constantly  present  in  fresh  venom,  but  have 
nothing  to  do  with  its  virulence. 

3.  Venoms  may  be  dried  and  preserved  indefinitely  in  this  condition  with  but 
very  slight  impairment  of  their  toxicity.     In  solution  in  glycerine  they  will  also 
probably  keep  for  any  length  of  time. 

4.  There  probably  exist  in  all  venoms  representatives  of  two  classes  of  proteids, 
globulins  and  peptones,  which  constitute  their  toxic  elements;  the  former  may  be 
represented  by  one  or  more  distinct  principles. 

5.  When  venom  is  taken  into  the  stomach  in  the  intervals  of  digestion,  enough 
of  the  poison  may  be  absorbed  to  produce  death,  especially  in  the  case  of  those 
venoms  which  contain   a  larger  proportion  of  the  more  dialysable  peptone ;   but 
during  active  digestion  the  venom  undergoes  alteration  and  is  rendered  harmless. 

6.  Potassic  permanganate,  ferric  chloride  in  the  form  of  the  liquor  or  tincture, 
and  tincture  of  iodine  seem  to  be  the  most  active  and  promising  of  the  generally 
available  local  antidotes. 

7.  Venom  exerts  a  powerful  local  effect  upon  the  living  tissues,  and  induces 
more  rapid  necrotic  changes  than  any  known  organic  substance.    It  causes  cedema, 
swelling,  attended  with  darkening  of  the  parts  by  infiltration  of  incoagulable  blood, 
breaking  down  of  the  tissues,  putrefaction,  and  sloughing. 

8.  It  renders  the  blood  incoagulable. 

9.  When  brought  in  contact  with  a  vascular  tissue  of  a  warm-blooded  animal 
it  produces  such  a  change  in  the  capillary  bloodvessels  that  their  walls  are  unable 
to  resist  the  normal  blood  pressure,  thus  allowing  the  blood-corpuscles  to  escape 
into  the  tissues.     These  lesions  are,  however,  not  analogous  to  those  of  inflamma- 
tion, since  in  the  latter  process  it  is  principally  the  white  blood-corpuscles  which 
emigrate  from  the  vessels,  and  the  blood  is  highly  coagulable,  while  here  the  blood 
exudes  en  masse  and   coagulates  with   difficulty,  if  at  all.     Free   access  of  air 
(probably  of  oxygen)  appears  to  lessen  the  virulent  effects.     The  mesentery  exposed 
to  air,  and  on  which  the  venom  is  merely  brushed,  endures  the  venom  longer  and 
in  much  larger  quantity  than  when  the  poison  is  injected  into  the  unopened  and 


GENERAL   CONSIDERATIONS.  155 

uninjured  peritoneal  cavity,  or  when  directly  throAvn  into  the  blood.     There  may 
be  here  also  a  question  of  temperature  and  other  conditions. 

The  following  facts  as  elicited  in  these  investigations  seem  to  be  sufficient  to 
explain  the  mechanism  of  the  hemorrhages:  the  blood  pressure  has  been  shown 
to  play  a  most  important  part;  a  watery  salt  solution  substituted  for  the  blood  does 
not  extravasate,  hence,  blood  seems  to  be  necessary ;  there  always  occur  molecular 
changes  in  the  bloodvessel  walls  from  the  effect  of  venom.  That  blood  pressure  is  an 
important  factor  has  been  established  by  the  observation  that  the  hemorrhages  as  a 
rule  occur  first  in  the  capillaries  which  are  immediately  next  to  or  nearest  the  large 
bloodvessels.  The  hemorrhages  take  place  soonest  where  the  force  of  the  blood 
current  is  first  felt  and  cannot  be  sufficiently  resisted,  and  in  no  case  do  hemor- 
rhages seem  to  originate  from  vessels  with  strong  walls  like  the  arterioles  or  veins. 
Cutting  off  the  circulation  of  a  part,  as,  for  instance,  by  ligation  of  the  vessels  of 
the  mesentery,  destroys  the  blood  pressure,  and,  as  a  consequence,  the  hemorrhages 
are  so  slight  as  scarcely  to  be  seen  by  the  naked  eye  though  venom  was  freely 
applied.  Finally,  the  colloid,  softened,  diffluent  condition  of  the  red  corpuscles 
must  inevitably  facilitate  extravasations.  It  is  impossible  to  have  seen  numerous 
cases  of  venom  poisoning  without  noting  a  variety  of  symptoms  often  abrupt  or 
unexpected.  These  often  are  due,  as  Dr.  Mitchell  long  since  pointed  out,  to  acci- 
dental hemorrhages  into  brain,  kidney,  and  heart  tissues.  They  explain  much 
which  might  otherwise  seem  inscrutable,  and  serve  sometimes  to  give  a  marked 
individuality  of  symptoms  to  cases  which  survive  long. 

10.  Among  the  most  remarkable  effects  of  venom  is  that  upon  the  red  blood- 
corpuscles.     These  bodies  undergo  substantial  modifications,  i.  e.,  they  lose  their 
bi-concave  shape,  become  spherical  and  softened,  and  fuse  together  into  irregular 
masses  acting  like  soft  elastic  colloid  material.     This  jelly-like  condition  of  the 
corpuscles  is  no  doubt  doubly  important:  in  connection  with  the  extravasation  of 
the  blood,  and  in  its  probable  interference  with  the  normal  respiratory  functions  of 
the  blood-cells. 

11.  The  direct  action  of  venom  upon  the  nervous  system  save  as  concerns  the 
paralysis  of  the  respiratory  centres  is  of  but  little  importance. 

12.  The  alterations  in  the  pulse-rate  are  dependent  chiefly  upon  two  antagonistic 
factors  which  are  active  at  the  same  time,  the  one  tending  to  increase  the  rate  and 
the  other  to  diminish  it.     The  former  is  found  in  the  increased  activity  of  the 
accelerator  centres  and  the  other  in  a  direct  action  on  the  heart.     When  we  have  the 
action  on  the  accelerator  centres  removed  by  isolation  of  the  heart  from  any  centric 
influence  we  almost  invariably  find  a  diminution  of  the  heart  beats.     Occasionally 
after  this  operation  the  pulsations  are  increased,  but  this  alteration  is  attended,  as 
in  the  case  of  the  diminution  of  the  pulse,  by  feeble  heart  beats,  and  accordingly 
is  but  a  manifestation  in  another  way  of  a  depressed  condition  of  the  heart. 

13.  The  variations  in  arterial  pressure  are  due  chiefly  to  three  causes,  depression 
of  the  vaso-motor  centres,  depression  of  the  heart,  and  irritation  and  consequent 
constriction  or  blocking  up  of  the  capillaries.     It  seems  not  improbable  that  all  of 
these  are  consentaneously  active,  and  it  therefore  follows  that  such  alterations  are  de- 
pendent upon  the  relative  degree  of  power  exerted  by  any  one  of  these  factors.     Our 


156  THE    VENOMS    OF    CERTAIN    THANATOPHIDE^E. 

results  indicate  that  the  profound  primary  fall  of  arterial  pressure  is  chiefly  due  to 
depression  of  the  vaso-motor  centres  and  is  in  part  cardiac,  that  the  subsequent 
recovery  is  capillary,  while  the  final  fall  is  cardiac.  The  initial  fall  does  not  con- 
tinue, because  the  constriction  of  the  capillaries  is,  for  a  time  at  least,  capable  of 
compensating  the  depressed  action  of  the  central  organ  of  circulation. 

14.  The  respirations  are  primarily  increased  and  secondarily  diminished.     Here 
again  we  have  two  antagonistic  factors  at  work  together,  one  tending  to  increase 
and  the  other  to  diminish  the  rate.     The  former  is  an  irritation  of  the  peripheries 
of  the  vagi  nerves  and  the  latter  a  depression  of  the  respiratory  centres  ;  whether  we 
have  an  increase   followed  by  a  decrease  or  a  decrease  from   the  first  will  depend 
upon  the  relative  intensity  of  the  action  of  the  venom  on  these  two  parts.     When 
the  action  of  the  venom  is  sufficient  to  profoundly  depress  the  centres  the  excitation 
of  the  peripheries  may  prove  futile. 

15.  Death   in  venom-poisoning  may  occur  through  paralysis  of  the  respiratory 
centres,  paralysis  of  the  heart,  hemorrhages  in  the  medulla,  or  possibly  through  the 
inability  of  the  profoundly  altered  red  corpuscles  to  perform  their  functions.     There 
can  be  no  question,  however,  that  the  respiratory  centres  are  the  parts  of  the  system 
most  vulnerable  to  venom,  and  that  death  is  commonly  due  to  their  paralysis. 

A  general  survey  of  the  chief  physiological  actions  of  venoms  leads  us  to  believe 
that  the  most  important  effects  are  upon  the  respiratory  and  circulatory  appara- 
tuses, and  that  in  the  production  of  these  results  antagonistic  factors  are  at 
work  so  that  we  sometimes  have  observations  which  seem  directly  contradictory. 
When  it  is  remembered  that  there  are  two  classes  of  poisons  in  venoms,  that  each 
class  possesses  certain  distinguishing  physical,  chemical,  and  physiological  differ- 
ences, although  closely  related,  it  is  easy  to  conceive  of  the  cause  of  the  existence 
of  antagonistic  actions  and  the  necessarily  varying  results. 

A  comparative  study  of  the  actions  of  the  globulins  and  peptones  indicates  that 
the  (jlobulins  produce  swelling  and  blackening  of  the  parts  by  infiltration  of  incoagu- 
lable blood ;  they  are  the  more  potent  in  producing  ecchymoses,  in  destroying  the 
coagulability  of  the  blood,  in  modifying  the  red-corpuscles,  and  in  the  production 
of  molecular  changes  in  the  capillary  walls  ;  their  action  on  the  accelerator  centres  of 
the  heart  is  more  notable  than  that  of  the  peptone,  hence  they  are  more  active  in 
causing  the  increased  pulse-rate ;  they  exert,  too,  a  more  marked  action  on  the  vaso- 
motor  centres  in  producing  the  primary  fall  of  pressure  and  are  the  greater  depres- 
sants of  the  heart ;  they  also  act  more  powerfully  upon  the  respiratory  centres  to 
paralyze  them.  The  peptones  are  more  active  in  the  production  of  oedema,  in  the 
breaking  down  of  the  tissues,  in  the  production  of  putrefaction  and  sloughing  ;  they 
have  little  power  to  produce  ecchymoses,  to  prevent  coagulation  or  modify  the  cap- 
illary walls  or  the  blood-corpuscles ;  they  have  less  tendency  to  accelerate  the  pulse  ; 
they  tend  to  increase  the  blood-pressure  by  irritating  the  capillaries,  and  are  the  prin- 
cipal factor  in  exciting  the  peripheries  of  the  vagi  nerves  in  the  production  of  the 
increased  respiration-rate. 

A  knowledge  of  these  peculiarities  in  the  actions  of  globulins  and  peptones  coupled 
with  the  fact  that  the  two  classes  exist  in  different  proportions  in  the  various 
species  of  venoms  is  of  great  importance  in  explaining  the  diverse  pathological 


GENERAL    CONSIDERATIONS.  157 

appearances  in  cases  of  poisoning  in  different  kinds  of  snake-bite — and  suggests 
immediately  the  cause  of  the  frightful  local  changes  which  are  seen  after  the  bite 
of  the  Crotalidae  hut  scarcely  at  all  in  Cobra-poisoning.  It  must  not,  however,  be 
supposed  that  the  peptones  or  globulins  for  instance  are  absolutely  identical  physio- 
logically iu  every  venom,  as  they  are  probably  modified  physiologically  as  well  as 
chemically,  although  we  do  not  doubt  that  on  the  whole  the  type  of  action  is 
carried  throughout  all  species.  Cobra  venom  does  not  produce  the  marked  lesions 
of  Crotalus-poisoning  because  it  is  so  lacking  in  globulins ;  it  is  weak  in  the  pro- 
duction of  the  local  swelling  and  blackening  of  the  parts,  of  the  ecchymoses,  of  the 
altered  corpuscles  and  of  the  non-coagulability  of  the  blood,  but  the  effects  of  Cobra 
venom  are  closely  in  accord  with  the  actions  peculiar  to  peptones.  The  peptone  of 
Cobra  seems  to  have  a  more  decided  power  in  producing  convulsions  than  that  of 
the  rattlesnake. 

The  fact  that  the  active  principles  of  venom  are  proteids,  and  closely  related 
chemically  to  elements  normally  existing  in  the  blood,  renders  almost  hopeless  the 
search  for  a  chemical  antidote  which  can  prove  available  after  the  poison  has 
reached  the  circulation,  since  it  is  obvious  that  we  cannot  expect  to  discover  any 
substance  which  when  placed  in  the  blood  will  destroy  the  deadly  principles  of 
venom  without  inducing  a  similar  destruction  of  vital  components  in  the  circu- 
lating fluid.  The  outlook  then  for  an  antidote  for  venom  which  may  be  available 
after  the  absorption  of  the  poison  lies  clearly  in  the  direction  of  a  physiological 
antagonist,  or,  in  other  words,  of  a  substance  which  will  oppose  the  actions  of  venom 
upon  the  most  vulnerable  parts  of  the  system.  The  activities  of  venoms  are,  how- 
ever, manifested  in  such  diverse  ways  and  so  profoundly  and  rapidly  that  it  does  not 
seem  probable  that  we  shall  ever  discover  an  agent  which  will  be  capable  at  the 
same  time  of  acting  efficiently  in  counteracting  all  the  terrible  energies  of  these 
poisons. 

It  is  now  most  desirable  that  our  discovery  of  the  complex  chemical  nature  of 
venoms  should  be  made  the  groundwork  in  India  of  a  study  of  the  poison  of  the 
Bungarus,  the  Daboia,  and  especially  of  the  dangerous  Hydrophidea?.  So  far  all 
efforts  on  our  part  to  obtain  the  venoms  of  Australian  and  South  American  snakes 
have  failed,  so  that  these  and  the  dreaded  Vipere  Fer-de-lance  and  the  large  Elaps 
of  Mexico  remain  so  far  really  unstudied. 


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DESCRIPTION  OF  PLATES. 


PLATE     I. 

Fig.  1. — Poisoning  by  venom  peptone  of  Crotalus  adamanteus.  Local  appearances  on  section 
after  death. 

Fig.  2. — Poisoning  by  venom  peptone  of  Crotalus  adamanteus.  Local  appearances  after  death 
and  before  laying  the  part  open.  The  oederaatous  prominent  swelling  is  well  shown,  but  is 
made  rather  too  darkly  red. 

Fig.  3. — Local  effects  of  venom  peptone,  when  the  poisoning  is  chronic.  The  grayish  serai-gangre- 
nous muscles  are  shown  in  contrast  with  the  uninjured  muscle  of  the  opposite  side. 


PLATE    II. 

Fig.  1. — Extensive  local  lesions  after  death  from  venom  globulin  (dialysis  globulin).    From  Crotalus 

Adamanteus  venom. 

Fig.  2. — Local  lesions  after  death  from  a  solution  of  dry  Cobra  venom — rabbit. 
Fig.  3. — Contrast  with  Fig.  2  the  profound  local  change  caused  in  a  rabbit  by  venom  of  Crotalus. 

In  both  cases  fatal  results  took  place  in  two  hoars,  the  doses  having  been  small. 


PLATE    III. 

Figs.  1  and  2  exhibit  the  increased  adhesiveness  of  human-blood  globules  when  the  fresh  blood  has 

been  mixed  with  fresh  venom. 
Fig.  3. — Naked-eye  view  of  loop  of  mesentery  in  a  cat  showing  effects  of  local  application  of  venom 

of  Crotalus.     Extensive  hemorrhages  separate  the  two  peritoneal  layers,  and  are  seen  to  have 

oozed  through  them  freely. 

Fig.  4. — First  microscopic  appearances  of  hemorrhage  from  capillaries  of  mesentery  of  cat. 
Figs.  5,  6,  7. — Successive  stages  of  increasing  loss  of  blood. 


PLATE    IV. 

Microscopic  appearances  of  human  blood  on  being  mixed  with  fresh  venom.  The  alteration  in  form 
and  the  elasticity  and  adhesiveness  are  well  shown  in  Fields  1,  2,  and  3 — Photographs  by  Dr. 
Geo.  A.  Piersol. 

PLATE   V. 

Extensive  hemorrhag-ic  lesions  in  abdominal  organs  of  etherized  rabbit  poisoned  by  intra-peritoneal 
injection  of  venom  of  Crotalus  adamanteus. 

(181) 


TE    1. 


Pift.l. 


Fig.  2. 


T.Sinc' 


PLATE   111. 


Fife  1 


PLATE   IV. 


Fig.  3. 


PLATE  V. 


1 


INDEX. 


A. 


Absorption  of  venom,  45,  154. 

Acid,  acetic,  effect  of,  on  toxicity  of  venom,  35. 

Acid,  bromohydric,  effect  of,  on  toxicity  of  venom, 
31,  43. 

Acid,  hydrobromic,  effect  of,  on  toxicity  of  venom, 
35,  43. 

Acid,  muriatic,  effect  of,  on  toxicity  of  venom,  34. 

Acid,  nitric,  effect  of,  on  toxicity  of  venom,  33. 

Acid,  sulphuric,  effect  of,  on  toxicity  of  venom, 
34. 

Acid,  tannie,  effect  of,  on  toxicity  of  venom,  36. 

Active  principles  of  venom,  9,  157. 

Activity  of  venom  when  applied  to  mucous  sur- 
faces, 44,  148;  when  applied  to  serous  sur- 
faces, 45,  149. 

Age,  effects  of,  on  toxicity  of  venom,  21. 

Agents,  effects  of  various,  on  the  toxicity  of 
venom,  21. 

Alcohol,  absolute,  effects  of,  on  toxicity  of  venom, 
29. 

Alcohol,  effects  of,  on  toxicity  of  venom,  27. 

Alkalies,  effects  of,  on  toxicity  of  venom,  29. 

Alkaloids  suspected  in  venom,  9. 

Alum,  effects  of,  on  toxicity  of  venoms,  36. 

Ammonia,  effects  of,  on  toxicity  of  venoms,  32. 

Analysis  of  venoms — see  chemistry  of  venoms. 

Antidotes,  local,  21,  43,  154,  157. 

Appearances  of  venom  when  dried,  5. 

Argentic  nitrate,  effects  of,  on  toxicity  of  venoms, 
39. 

Arterial  pressure,  action  of  pure  venoms  upon, 
85-102. 

Arterial  pressure,  action  of  venom  globulins  upon, 
102-112. 

Arterial  pressure,  action  of  venom  peptones  upon, 
112-118. 

Artificial  digestion,  effect  of,  on  toxicity  of 
venoms,  42. 


B. 

Bacteria  in  venom,  6,  7,  133,  135,  136,  154. 
Bile,  effect  of,  on  toxicity  of  venom,  42. 
Blood  clot,  peculiarities  of,  caused  by  venom,  142. 
Blood  corpuscles,  action  of  fresh  venom  upon, 

143,  155. 
Blood   corpuscles,  disintegration  of,  by  venom, 

141,  145. 
Blood,  effect  of  venom  poisoning  on,  138,  139, 

140,  141. 

Blood,  extravasations  of,  138-140,  146,  148,  154. 
Bloodvessel   walls,  effect  of  venom   upon,   146, 

150,  154. 
Boiled  solution  of  venom,  difficulties  in  filtering 

clear,  13,  17. 

Boiling,  effect  of,  on  venom,  17,  26,  46,  47,  51. 
Bouillon,  putrefaction  experiments  with,  134. 
Brain,  effect  of  venom  upon,  148. 
Bromine,  effect  of,  on  toxicity  of  venom,  37. 
Bromohydric  acid,  effect  of,  on  toxicity  of  venom, 

37. 

C. 

Care  of  serpents,  2. 

Caustic  alkalies,  effects  of,  on  toxicity  of  venoms, 

29. 
Caustic  potash,  effects  of,  on  toxicity  of  venoms, 

29. 

Chemistry  of  venoms,  9,  153. 
Ciliary  motion,  action  of  venom  upon,  149. 
Clot,  blood,  peculiar  characters  of,  142. 
Coagulation  of  blood,  action  of  venom  globulin 

upon,  142. 
Coagulation  of  blood,  action  of  venom  peptone 

upon,  142. 
Coagulation    of  blood,   action  of  venom   upon, 

138-141. 

Color  of  venom,  5. 

Coloring  matter  of  venom,  how  separated,  7,  8. 

(183) 


184 


INDEX. 


Comparative  local  effects  of  different  venoms, 
55,  157. 

Copper-venom-globulins,  action  on  pulse-rate, 
69-79. 

Copper-venom-globulins,  action  on  arterial  press- 
ure, 102-112. 

Copper-venom-globulins,  action  on  respiration, 
125-130. 

Copper-venom-globulins,  comparative  reactions 
of,  19. 

Copper-venom-globulins,  local  actions  of,  54. 

Copper-venom-globulins,  method  of  preparation, 
11,  153. 

Copper-venom-globulins,  proportion  in  venom,  20. 

Copper-venom-globulins,  reactions  of,  12,  15. 

Cornea,  the  action  of  venom  upon,  148. 

Culture  experiments  with  venom,  136. 

D. 

Daboia  venom,  19,  55,  63,  92. 
Death,  cause  of,  in  venom  poisoning,  156. 
Death,  time  of  the  occurrence  of,  139-140. 
Desiccation  of  venom,  effects  of,  on  toxicity  of 

venom,  21. 
Dialysis-venom-globulin,  action  of,  on  pulse-rate, 

69-79. 
Dialysis-venom-globulin,    action   of,    on    arterial 

pressure,  102-112. 
Dialysis-venom-globulin,  action  of,  on  respiration, 

125-130. 

Dialysis-venom-globulin,  local  action  of,  54. 
Dialysis-venom-globulin,  method  of  preparation, 

12. 

Dialysis-venom-globulin,  proportion  in  venom,  20. 
Dialysis-venom-globulin,  reactions  of,  12,  13,  15. 
Dialyzed  iron,  effects  of,  on  toxicity  of  venom,  40. 
Difficulties  attending  researches  with  venom,  1. 
Digestion  of  venoms,  effects  of,  on  toxicity  of 

venoms,  22. 

Dry  heat,  effects  of,  on  toxicity  of  venoms,  22. 
Drying  venoms,  loss  in,  8. 

E. 

Ecchymoses — see  hemorrhages. 
Epithelium  in  venom,  6,  7. 

F. 

Ferric   chloride,    effects   of,    on   the   toxicity   of 

venom,  40. 
Ferrous  sulphate,  effects  of,  on  the  toxicity  of 

venom,  39. 


Filtration  experiments  with  fresh  venom  to  study 

morphological  constituents,  133. 
Filtration  of  venom  through  various  substances, 

effects  on  the  toxicity  of  venom,  42. 

G. 

Globulins — see  venom  globulins. 

Granular  matter  in  muscular  tissue  produced  by 

venom,  141,  146. 
Granular  matter  in  venoms,  6,  133. 

H. 

Hemorrhages  from  venom  poisoning,  139,  140, 

146,  148,  154. 

Hemorrhages,  mechanism  of,  149-152,  155. 
Heat,  effects  of,  on  toxicity  of  venom,  35. 
Heated  venom,  experiments  with,  134. 
Hydrobromic    acid,    effects    of,    on    toxicity   of 

venom,  35. 


I. 

Insoluble  precipitate  in  venom,  9. 

Insoluble  precipitate  in  venom,  general  characters 

of,  10,  154. 
Iodine  and  potassic  iodide,  effects  of,  on  toxicity 

of  venom,  37. 

Iodine,  effects  of,  on  toxicity  of  venom,  37,  43. 
Iron,  liquor  chloride  of,  effects  of,  on  toxicity  of 

venom,  41,  43,  154. 
Iron,  tincture  of  chloride  of,  effects  of,  on  toxicity 

of  venom,  41,  43,  154. 

L. 

Lesions  from  venom,  macroscopical,  51,  137,  139, 

140,  154. 
Lesions  from  venom,  microscopical,  6,  133,  141, 

14*5,  146. 
Liquor   ferri    chlor.,    effect   on    the    toxicity   of 

venom,  41,  43,  154. 
Loss  in  drying  venom,  8. 
Lungs,  alterations  in,  by  venom,  139-141,  147. 

M. 

Macroscopical  appearances  produced  by  venom, 

51,  137,  139,  140,  154. 
Medulla,  alterations  in,  148. 
Mercuric    chloride,    effect   of,    upon    toxicity   of 

venom,  39. 
Mesentery,  action  of  venom  upon,  149. 


INDEX. 


185 


Micrococci  in  venom,  fi,  136,  154. 
Microscopical    appearances  produced  by  venom, 

6,  133,  141,  145,  140. 

Moist  beat,  effect  of,  on  toxicity  of  venom,  22-27. 
Morphological  constituents  of  venom,  138. 
Motion,  ciliary,  action  of  venom  upon,  14!). 
Motor  nerves,  action  of  venom  upon,  49. 
Mucous  surfaces,  action  of  venom  upon,  44,  148. 
.Muriatic  acid,  effects  of,  upon  toxicity  of  venoms, 

33. 

Muscular  tissues,  dry  atrophy  of,  140. 
Muscular   tissues,  putrefaction   experiments   on, 

135. 


N. 


Necrotic  changes  caused  by  venom,  135,  154. 
Nerves,  motor,  effects  of  venom  upon,  49. 
Nerves,  sensory,  effects  of  venom  upon,  49. 
Nervous  system,  effects  of  venom  upon,  48,  155. 
Neutralization  of  venom,  result  of,  9. 


P. 


Pathology  of  serpent  venoms,  133-152. 

Peptone — see  venom  peptone. 

Peroxide  of  hydrogen,  effect  of,  on  toxicity  of 

venom,  39. 

Physical  characteristics  of  venom,  5. 
Plan  of  isolation  of  poisons,  defects  in,  153. 
Plan  of  study,  defects  in,  153. 
Poisoning,  chronic,  140. 
Poisoning,  rapid,  137. 
Potash,  effects  on  toxicity  of  venom,  29. 
Potassic  iodide,  effects  on  toxicity  of  venom,  38. 
Potassic  iodide  and  iodine,  effects  on  toxicity  of 

venom,  37. 
Potassic    permanganate,    effects   on   toxicity   of 

venom,  38,  43,  153. 
Preservation  of  venom,  5. 

Pressure,  arterial  or  blood — see  arterial  pressure. 
Proteid  constituents  of  venoms,  19,  20. 
Pulse-rate,  action  of  pure  venoms  upon,  56-69, 

155. 
Pulse-rate,  action  of  venom  globulins  upon,  69-79, 

156. 
Pulse-rate,  action  of  venom  peptones  upon,  79-84, 

156. 

R. 

Reaction  of  venoms,  9. 
Reactions  of  copper-venom-globulins,  12,  15. 
Reactions  of  dialysis-venom-globulins,  12,  13,  18. 
Reactions  of  water-venom-globulins,  11,  14, 17, 18. 

24         July,  1886. 


Reactions  of  venom  peptones,  10,  13,  15,  18. 
Respiration,  action  of  pure  venoms  upon,  119-125. 
Respiration,   action    of   venom    globulins    upon, 

125-130,  156. 
Respiration,    action   of   venom    peptones   upon, 

130-132,  156. 

S. 

Saliva,  analogy  of  venoms  to,  154. 
Salts  in  venom,  20. 

Sensory  nerves,  action  of  venom  upon,  49. 
Serpent  loop,  2. 
Serpents,  care  of,  2. 
Serpents,  feeding  of,  2. 
Serous  surfaces,  effects  of  venom  on,  45,  149. 
Silver  nitrate,  effect  upon  toxicity  of  venom,  39. 
Snake  bile,  effect  upon  toxicity  of  venom,  42. 
Snake  loop,  2. 

Sodic  hydrate,  effect  upon  toxicity  of  venom,  32. 
Solids  in  venom,  5,  6,  133,  154. 
Specific  gravities  of  venoms,  8. 
Spermatozoa,  effects  of  venom  upon,  149. 
Spinal  cord,  effects  of  venom  upon,  49. 
Sulphuric  acid,  effects  of,  upon  the  toxicity  of 
venoms,  34. 


T. 


Tannic   acid,    effects   of,    upon    the    toxicity   of 

venoms,  36. 
Tincture  of  the  chloride  of  iron,  effects  of,  upon 

the  toxicity  of  venoms,  41,  43. 
Toxic  elements  in  venom,  154. 


V. 


Venom  globulins,  10. 

Yenom  globulins,  action  on  pulse-rate,  69-79, 156. 

Venom  globulins,  action  on  arterial  pressure, 
102-112,  156. 

Venom  globulins,  action  on  respirations,  125- 
130,  156. 

Venom  globulins,  comparative  reactions  of,  14, 
16,  18,  19. 

Venom  globulins  compared  with  venom  peptones 
lexicologically,  51,  118,  142,  156. 

Venom  globulins,  defects  in  method  of  prepara- 
tion, 153. 

Venom  globulins,  distinguishing  features  of  vari- 
ous, 13,  14,  16,  18,  19. 

Venom  globulins,  general  characters  of,  10. 

Venom  globulins,  how  held  in  solution  in  venoms, 
12. 


186 


INDEX. 


Venom  globulins,  how  prepared,  10. 

Venom  globulins,  local  actions  of,  53. 

Venom  globulins,  physiological  peculiarities  of, 

47,  142,  156 

Venom  globulins,  proportions  in  venoms,  20. 
Venom  globulins,  reactions  of,  10. 
Venom  globulins,  toxicity  affected  by  boiling,  55. 
Venom  globulins,  toxicity  affected  by  drying,  53. 
Venom  peptones,  10. 
Venom    peptones,   action  on  pulse-rate,   79-84, 

156. 
Venom    peptones,    action    on    arterial    pressure, 

112-118,  156. 
Venom  peptones,  action  on  respiration,  130-132, 

156. 

Venom  peptones,  comparative  reactions  of,  19. 
Venom  peptones  compared  with  venom  globulins 

toxicologically,  51,  118,  142,  156. 
Venom  peptones,  general  characters  of,  10,  17, 

19. 

Venom  peptones,  how  prepared,  10,  13. 
Venom  peptones,  local  actions  of,  51. 
Venom  peptones,  peculiar  characters  of,  11,  17. 
Venom  peptones,  physiological  peculiarities  of, 

47,  156. 


Venom  peptones,  proportions  of,  in  venom,  20. 
Venom  peptones,  reactions  of,  10,  13,  15,  18. 
Voluntary  motion,  effect  of  venom  upon,  49. 


W. 


Water-venom-globulins, 
Water- venom-globulins, 

69-79. 
Water- venom-globulins, 

pressure,  102-112. 
Water-venom-globulins, 

tions,  125-130. 
Water-venom-globulins, 

18.- 

Water-venom-globulins, 
Water-venom-globulins, 
Water-venom-globulins, 
Water-venom-globulins, 


10,  14,  16. 

action  on  the  pulse-rate, 

action  on  the  arterial 
action  on  the  respira- 
comparative  reactions, 

how  prepared,  10. 
local  action,  54. 
proportion  in  venoms,  20. 
reactions  of,  11,  14,  17. 


Y. 


Yellow  pigment  of  venom,  6,  7,  8. 

Yellow  pigment  of  venom,  separation  of,  7,  8. 


V 


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